Home Utilization of zein nano-based system for promoting antibiofilm and anti-virulence activities of curcumin against Pseudomonas aeruginosa
Article Open Access

Utilization of zein nano-based system for promoting antibiofilm and anti-virulence activities of curcumin against Pseudomonas aeruginosa

  • Shaimaa M. Badr-Eldin , Hibah Mubarak Aldawsari , Osama A. A. Ahmed , Sabna Kotta , Walaa Abualsunun , Bayan A. Eshmawi , El-Sayed Khafagy , Samar S. Elbaramawi , Hisham A. Abbas , Wael A. H. Hegazy EMAIL logo and Noura M. Seleem
Published/Copyright: March 11, 2024
Download Article (PDF)
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Nanotechnology Reviews
From the journal Nanotechnology Reviews Volume 13 Issue 1

Abstract

Bacterial biofilms contribute to increased pathogenesis and bacterial resistance. Biofilms can enhance pathogenicity by shielding bacteria from the immune system and antibiotics, and they are associated with persistent infections. Additionally, the antibiotic resistance mechanisms within biofilms make them challenging to treat, emphasizing the need for strategies to be addressed. Mitigating bacterial virulence is a promising strategy that could ease their eradication by host immunity without stressing bacteria to induce resistance. The merits of this strategy are augmented when using safe anti-virulence candidates in proper formulations. The current study aimed to evaluate the antibiofilm and anti-virulence efficacy of curcumin–zein nanoparticles against Pseudomonas aeruginosa. In vitro investigations were performed to assess the effect of nanoparticles on biofilm formation, bacterial motility, and production of virulence factors, including proteases, hemolysins, and pyocyanin, in comparison to bulk curcumin. Furthermore, the effect on the expression of the genes that encode quorum sensing (QS) systems that regulate bacterial virulence was assessed. An in silico study was done to evaluate the affinity of curcumin to QS receptors. Additionally, an in vivo protection assay was performed to evaluate the inhibitory effect of our preparation on diminishing the P. aeruginosa’s capacity to induce pathogenesis. The results showed significant antibiofilm and anti-virulence activities of the curcumin–zein nanoparticles compared to bulk curcumin. These anti-virulence activities were attributed to the curcumin’s interfering with the P. aeruginosa QS systems that regulate its virulence. In conclusion, curcumin acquires significant anti-QS, anti-virulence, and antibiofilm activities that are vastly enhanced upon loading on zein nanoparticles.

Graphical abstract

Keywords: curcumin; zein nanoparticles; bacterial biofilms; antibiotic resistance; healthcare; Pseudomonas aeruginosa

1 Introduction

The rapid spread of antibiotic resistance in bacteria worldwide has become a significant concern for public health. Multiple studies have highlighted the alarming increase in illness and death rates linked to the growing prevalence of multidrug-resistant bacterial pathogens [1,2,3]. Bacterial biofilms can significantly contribute to bacterial resistance [4,5]. Biofilms are complex three-dimensional structures formed by clusters of bacterial cells surrounded by extracellular polymeric substances [6,7]. The complex structure and behavior of bacterial biofilms create a formidable challenge for antibiotic treatments [8,9,10,11,12]. Epidemiological research has notably identified biofilms as significant contributors to hospital-acquired infections [7,13,14,15,16]. This resistance mechanism is of particular concern in chronic infections associated with biofilm formation, such as those involving medical devices, wounds, and implant-related infections [14,17,18]. Addressing biofilm-related resistance often requires strategies that target both the biofilm matrix and the bacteria within the biofilm to achieve effective treatment [6,19,20].

Bacterial virulence is a multifactorial phenomenon, and it arises from the expression of various regulatory systems, notably quorum sensing (QS) systems. These QS systems play a pivotal role in coordinating and controlling the virulence behaviors of bacteria [21,22]. The QS systems intricately coordinate bacterial virulence through the secretion of specialized signaling molecules referred to as autoinducers [23,24]. In Gram-negative bacteria, QS systems mainly rely on N-acyl-homoserine lactones as signaling molecules that bind to their cognate receptors, forming autoinducer/receptor complexes that could control the expression of diverse virulence factors [21,25]. Studies have convincingly demonstrated the crucial roles of QS systems in the formation of bacterial biofilms and orchestrating the synchronized secretion of virulence factors [26,27]. Pseudomonas aeruginosa is a Gram-negative bacterium responsible for a broad spectrum of severe opportunistic infections [28,29,30]. In addition to its notable capability to develop antibiotic resistance, P. aeruginosa possesses an extensive array of virulence factors [3,31,32,33]. The QS systems of P. aeruginosa play the main role in controlling the expression genes that encode diverse virulence factors and are involved in biofilm formation [34,35,36].

In the dwindled supply of novel antibiotics against the continuous increase in bacterial resistance, there is a growing need to identify new drug targets and create innovative therapeutic strategies for addressing bacterial infections [37,38,39]. One of the most promising strategies involves reducing bacterial virulence without exerting pressure on bacteria to develop resistance [40,41,42,43]. This can be achieved by targeting the main virulence-controlling systems, namely QS systems [37,44,45,46]. Given this context, natural antimicrobial compounds extracted from plants have gained significant recognition as viable alternatives to traditional antimicrobials and antibiotics [42,47,48,49,50,51]. The antimicrobial, anti-biofilm, and anti-QS properties of secondary metabolites found in plants such as curcumin offer a promising avenue for combating bacterial infections [52,53]. Curcumin, a natural compound found in turmeric, has demonstrated antimicrobial activities against a wide range of microbes, including bacteria, fungi, and some viruses [54,55].

It is important to note that while curcumin shows promise as an antimicrobial, antibiofilm, and anti-virulence agent, its efficacy can vary depending on factors like concentration and formulation [56,57]. Therefore, the appropriate formulation of curcumin has the potential to ensure effective antibacterial and antibiofilm activity. The formulation process can enhance curcumin’s stability, bioavailability, and ability to interact with microbial cells and biofilms, ultimately improving its antimicrobial properties for various applications. For instance, curcumin nanoparticle formulations offer a promising avenue in the development of potential antimicrobials overcoming challenges associated with traditional antibiotics delivery into the biofilm matrices [58,59].

In the current study, curcumin has been formulated as zein nanoparticles using a modified liquid–liquid phase separation technique. The prepared nanoparticles were characterized for size and zeta potential. The objective of the current study is to evaluate the effectiveness of the prepared curcumin–zein nanoparticles in eliminating biofilms and reducing the virulence of P. aeruginosa.

2 Materials and methods

2.1 Materials

The chemicals were of pharmaceutical grade and obtained from Sigma-Aldrich (St. Louis, MO, USA). All microbiological media were procured from Oxoid (Hampshire, UK). P. aeruginosa PAO1 strain was utilized in this research.

2.2 Preparation of curcumin–zein nanoparticles

The modified liquid–liquid phase separation technique, previously described by Algandaby et al. [60], was adopted for preparing curcumin–zein nanoparticles in a ratio of 1:1 w/w. In brief, an ultrasonic probe (Vibra-Cell VCX 750; Sonics and Materials, Inc., Newtown, CT, USA) was utilized to dissolve accurately weighed equal amounts of curcumin (10 mg, in 15 m absolute ethanol) and Zein (10 mg, in 15 m 80% ethanol). The resulting solution was added to 30 mL deionized water, and the formed dispersion was agitated at 3,000 rpm at ambient temperature for 2 h. After complete ethanol evaporation, the aqueous dispersion was subjected to ultra-centrifugation at 20,000g and then lyophilized for 48 h.

2.3 Size and zeta potential measurements

After proper dilution with double distilled water, the size (z-average) and zeta potential of the prepared Curcumin-zein nanoparticles were determined using dynamic light scattering and electrophoretic techniques, respectively, using Malvern Zetasizer (Nano Z5P, Malvern Panalytical Ltd, United Kingdom). The results were expressed as the mean value of three replicates.

2.4 Detection of minimum inhibitory concentrations (MICs)

The MICs were determined using the microtiter plate broth dilution method according to Clinical Laboratory and Standards Institute guidelines [43,61]. The influence of the tested preparations on bacterial growth was assessed by measuring the optical density of P. aeruginosa cultures with or without the tested preparations as described [62,63].

2.5 Determination of antibiofilm activity

The inhibition of biofilm formation was evaluated using the crystal violet method as detailed [40,42]. Bacterial suspensions were prepared from an overnight culture in tryptic soya broth (TSB), and its optical density was adjusted to OD600 of 0.4 (equivalent to 1 × 108 CFU/mL). Subsequently, 10 μL aliquots of the suspension were introduced into 1 mL of fresh TSB, with and without tested preparations at sub-MIC. Portions of 100 μL of TSB, both with and without tested preparations, were dispensed into the wells of a 96-well microtiter plate and incubated at 37°C for 24 h. After incubation, planktonic cells were aspirated, and the wells were subjected to three washes with distilled water before being left to dry. The attached cells were then fixed with methanol for 15 min, followed by staining with a 1% crystal violet solution for an additional 15 min. Post-staining, the wells were washed, and the elution of the attached dye was carried out using 33% glacial acetic acid. The absorbance was measured at 590 nm.

To visualize the biofilm inhibition, bacterial biofilms were allowed to be formed on glass slides positioned in polystyrene petri plates, both in the presence and absence of tested preparations. Incubation of the plates took place for 24 h at 37°C. Post-incubation, the slides underwent a triple wash with water and were subsequently stained with crystal violet (1%) for a duration of 20 min. The stained slides were scrutinized under a light microscope at 100× magnification.

2.6 Detection of anti-virulence activity

2.6.1 Effect on bacterial motility

The P. aeruginosa swarming motility was evaluated on Muller Hinton (MH) agar plates (1.5% agar) provided with tested preparations, and the zones of motility were measured as demonstrated [43,49].

2.6.2 Anti-proteolytic activity

The inhibitory effect of tested preparations on protease production was evaluated using the skim milk agar method, as previously shown [47,62]. Luria–Bertani (LB) broth tubes, both with and without tested preparations at sub-MIC, were inoculated with P. aeruginosa and incubated overnight at 37°C. Upon centrifugation to collect supernatants, 100 µL of these supernatants were applied to wells created in skim milk agar plates (5%). Following an overnight incubation at 37°C, the clear zones resulting from proteolytic activity were measured.

2.6.3 Effect on hemolysins

The effect of the tested preparations on the activity of P. aeruginosa hemolysins was assessed as detailed in previous studies [63,64]. To conduct this evaluation, 0.5 mL of the prepared supernatants, as obtained in the protease assay, were combined with 0.7 mL of a fresh erythrocyte suspension in 2% saline and incubated at 37°C for 2 h. Subsequently, the absorbance of released hemoglobin resulting from lysed erythrocytes was measured at 540 nm in the separated supernatants obtained through centrifugation at 4°C. The released hemoglobin levels were compared with a positive control (0.1% SDS in erythrocyte suspension) and a negative control (erythrocytes in LB broth).

2.6.4 Effect on pyocyanin production

The production of P. aeruginosa virulent pigment was assessed both in the presence and absence of curcumin preparations, as previously demonstrated [40,50]. P. aeruginosa was cultivated in LB broth and incubated overnight, and the resulting bacterial suspension was adjusted to an OD of 0.4 at 600 nm. Subsequently, 10 μL of the prepared bacterial suspensions were introduced into LB broth tubes (1 mL) containing tested preparations at sub-MIC, as well as into control tubes. These tubes were then incubated at 37°C for 48 h. Following centrifugation to separate the supernatants, the inhibition of pyocyanin was evaluated by measuring the absorbance at 691 nm.

2.7 Effect on the expression of QS-controlling genes

The qRT PCR was used to quantify the expression of P. aeruginosa QS-encoding genes. The total RNA was extracted from bacterial cells treated or untreated with the tested preparations using Gene JET RNA Purification Kit (Thermo Scientific, USA) and kept at −80°C as described [43,65]. The encoding genes of the P. aeruginosa QS systems lasI/R, rhlI/R, and pqsA/R were amplified using the primers listed [43,66]. The amplification was carried out using SensiFAST™ SYBR® Hi-ROX OneStep Kit (Bioline, UK) using StepOne Real-Time PCR system (Applied Biosystem, USA). The housekeeping gene rpoD was used to normalize the relative expressions, and the comparative threshold cycle (∆∆Ct) method was employed to calculate the relative gene expressions [65,67].

2.8 Virtual affinity of curcumin to P. aeruginosa QS receptors

Crystal structures of P. aeruginosa LasR (PDB: 6MVN) [68], QscR (PDB: 6CC0) [69], and PqsR (PDB: 4JVD) [70] were obtained from the RCSB Protein Data Bank (https://www.rcsb.org/accessed on 7 February 2023). The protein structures were prepared utilizing the QuickPrep protocol of Molecular Operating Environment (MOE 2019.012). Curcumin structure was retrieved from PubChem database (https://pubchem.ncbi.nlm.nih.gov/accessed on 7 February 2023) as SMILES. Curcumin structure was energy minimized to 0.1 Kcal/mol/Ų gradient RMS. The docking process was performed with Alpha triangle placement through Amber10: EHT force field.

2.9 In vivo evaluation of the anti-virulence activity

To investigate the impact of the tested preparations on diminishing the P. aeruginosa pathogenesis, the mice protection assay was performed [41,43]. Four groups of 3-week-old albino mice, each containing five, were recruited. The first group was kept uninfected, and the second group was intraperitoneally injected with sterile phosphate buffer saline as negative control groups. The mice in the next group were injected with DMSO-treated P. aeruginosa as a positive control group. The last group was injected with P. aeruginosa treated with nanoparticle formulation at sub-MIC. After 5 days, the mice were humanely euthanized via cervical dislocation, and the kidney and liver tissues were extracted for histopathological examination as described previously [43,71].

2.10 Statistical analysis

The tests were done in triplicate, and the results were averaged. The findings are presented as mean ± SD. Statistical significance was assessed using one-way ANOVA, and the significance is considered when p < 0.05.

3 Results and discussion

3.1 Particle size and zeta potential of curcumin–zein nanoparticles

The prepared curcumin–zein nanoparticles showed an average size (z-average) of 380.93 ± 4.21 nm. The reported size in the nano-range highlights the capability of the proposed formulation to augment the anti-virulence properties of curcumin. Furthermore, the prepared formulation showed a high degree of homogeneity, as indicated by a low polydispersity index value of less than 0.1. Regarding the zeta potential, the prepared nanoparticles exhibited an average of −1.82 ± 0.065, indicating reduced liability for immune recognition of the proposed formulation, with consequent enhanced efficacy. Representative size distribution by intensity and zeta potential plots are shown in Figure 1a and b, respectively.

Figure 1 Particle size distribution (a) and zeta potential (b) of curcumin–zein nanoparticles.
Figure 1

Particle size distribution (a) and zeta potential (b) of curcumin–zein nanoparticles.

Particle size plays a pivotal role in delivery systems designed for anti-virulence and antibiofilm applications. Nano-delivery systems are generally reported to have sizes in the 1–1,000 nm range [72]. More specifically, a size of less than 500 nm is considered appropriate for drug delivery applications [73]. At the nanoscale, nanoparticles exhibit an increased surface area, allowing for greater contact with microbial cells, thereby enhancing interactions for improved antimicrobial activity [74]. Thus, the increased surface area is particularly significant in anti-virulence strategies, where disrupting virulence factors is essential for mitigating the severity of infections. The increased surface area facilitates the efficient binding of nanoparticles to virulence factors, impeding their function and reducing the pathogen’s ability to cause harm [74]. Furthermore, a major factor is the size-dependent toxicity of nanoparticles, wherein smaller particles exhibit higher toxicity due to their enhanced ability to interact with microbial components [75]. In antibiofilm applications, particle size reduction is crucial to stop and eliminate biofilm development. Biofilms pose challenges in terms of resistance to conventional antimicrobial treatments. Nanoparticles with appropriate sizes can penetrate biofilms more effectively, disrupting the matrix and the embedded microbial cells [76]. This enhanced penetration is crucial for the successful dismantling of biofilms and preventing their recurrence. Another important hurdle that can also be addressed by nanosystems is the development of microbial resistance. The multifaceted interactions of nanoparticles with microbial cells and biofilm matrices make it challenging for pathogens to develop resistance, enhancing the overall efficacy of anti-virulence and antibiofilm strategies [77].

In conclusion, the importance of nanosize for anti-virulence and antibiofilm applications lies in its ability to influence surface interactions, penetration, and resistance prevention. Harnessing these properties through controlling size in the nano-range offers promising solutions to combat virulence and biofilm-related hurdles.

The zeta potential of nanoparticles, reflecting their surface charge, plays a pivotal role in drug delivery systems, influencing critical aspects such as stability and immune recognition. Nanoparticles with a high absolute zeta potential exhibit increased electrostatic repulsion, preventing aggregation and ensuring the stability of colloidal suspensions [78]. Nevertheless, nanoformulation can exhibit stability even when possessing a low zeta potential. This is due to the presence of additional variables, such as steric stabilization, which can also contribute to the stability of the dispersion [79].

Furthermore, the zeta potential affects the inflammatory and immune response to nanoparticles, with a neutral or slightly negative zeta potential being associated with reduced immune recognition and less inflammatory response compared to positively charged ones [80,81]. It is reported that positive surface charge leads to quick adsorption by serum proteins, including immunoglobulins that tag them for clearance by the reticuloendothelial system; on the other hand, neutral or slightly negative charges helps in avoiding removal by such phagocytic system, thereby increasing the half-life of nanoparticles in the bloodstream and enhancing their potential for drug delivery applications [81]. In summary, careful manipulation of the zeta potential is integral to optimizing the stability and immunological characteristics of nanoparticles in drug delivery systems.

3.2 Effect on bacterial growth at sub-MICs

The nanoformulation significantly reduced the MIC of curcumin as it was 1.25 or 1 mg/mL for curcumin in bulk or zein, respectively, while the MIC of the curcumin nanoformulation was 0.5 mg/mL. These results highlight the potent antibacterial activity in comparison to other nanoparticle preparations. For instance, the MIC of silver–curcumin nanoparticles inhibited P. aeruginosa at 10 mg/mL [82].

The strategy of mitigating the virulence of bacteria is promising to combat bacterial resistance as it is rooted in the idea of not affecting bacterial growth to avoid inducing stress in the bacteria, which can lead to the development of resistance [83,84]. To exclude any influence on the growth of bacteria, the anti-virulence and anti-QS activities of curcumin in bulk or nanoformulation, or zein, were tested at sub-MICs (1/8 MIC). There were no significant differences between the optical densities of the P. aeruginosa cultures with or without the tested preparations. This indicates that any in vitro or in vivo activity is due to the effect of preparation on virulence and not due to the inhibition of bacterial growth; all further experiments were conducted at sub-MICs.

3.3 Inhibition of biofilm formation

Bacterial biofilm is a complex and structured community of bacteria that adhere to surfaces and are enclosed within a protective matrix of extracellular polymeric substances [26,85]. Biofilms can form on various surfaces, such as medical devices, tissues, and natural environments. These biofilms are responsible for a wide range of persistent and chronic infections, and they exhibit increased resistance to antibiotics and the host immune system compared to planktonic (free-floating) bacteria [86,87]. Therefore, one of the most significant objectives of developing new antimicrobial agents is the disruption of biofilms that can lead to improved treatment outcomes and reduced antibiotic resistance. In this context, various studies have explored the potential of nanoparticles in disrupting and eliminating biofilms, demonstrating their promising efficacy in combating persistent microbial communities that result in the destabilization of biofilms, prevent their reformation, and enhance the efficacy of conventional antimicrobial treatments [88,89]. This is due to the unique physicochemical properties of nanoparticles that enable them to interact with and penetrate biofilm matrices effectively. Their small size and large surface area-to-volume ratio facilitate enhanced penetration into biofilms, allowing them to directly target and disrupt the extracellular polymeric substances that encase biofilm communities [90,91,92].

The antibiofilm activities of the curcumin alone, curcumin in nanoformulation, and zein were performed at sub-MIC using the crystal violet method. However, zein increased the biofilm formation significantly (115%) in comparison to untreated bacteria, whereas curcumin alone or in nanoformulation significantly reduced the biofilm formation by 24 and 70%, respectively (Figure 2). Importantly, curcumin nanoformulation significantly diminished the biofilm formation compared to curcumin alone, which indicates the significant antibiofilm activity of the nanoformulation. The results of the percentages of virulence factor formation are summarized in Table 1.

Figure 2 Curcumin in nanoformulation acquires significant antibiofilm activity. The biofilm formation in the presence of curcumin alone and nanoformulation was compared to that formed with untreated bacteria and zein-treated bacteria using the crystal violet method at sub-MIC concentrations to exclude any influence on the growth. (a) Representative light microscope images for the effect on biofilm formation. Curcumin alone or in nanoformulation (at sub-MIC) obviously decreased the biofilm formation in comparison to biofilm formed by untreated P. aeruginosa PAO1. On the other hand, zein increased the biofilm formation markedly in comparison to untreated bacteria. (b) Quantification of biofilm formation. However, zein increased the biofilm formation significantly compared to untreated bacteria, while curcumin diminished significantly the biofilm formation. The most significant reduction in biofilm formation was observed with curcumin in nanoformulation (about 70%) than the curcumin effect alone (about 24%). **p < 0.01; ***p < 0.001.
Figure 2

Curcumin in nanoformulation acquires significant antibiofilm activity. The biofilm formation in the presence of curcumin alone and nanoformulation was compared to that formed with untreated bacteria and zein-treated bacteria using the crystal violet method at sub-MIC concentrations to exclude any influence on the growth. (a) Representative light microscope images for the effect on biofilm formation. Curcumin alone or in nanoformulation (at sub-MIC) obviously decreased the biofilm formation in comparison to biofilm formed by untreated P. aeruginosa PAO1. On the other hand, zein increased the biofilm formation markedly in comparison to untreated bacteria. (b) Quantification of biofilm formation. However, zein increased the biofilm formation significantly compared to untreated bacteria, while curcumin diminished significantly the biofilm formation. The most significant reduction in biofilm formation was observed with curcumin in nanoformulation (about 70%) than the curcumin effect alone (about 24%). **p < 0.01; ***p < 0.001.

Table 1

Percentage of the production of virulence factors

Virulence factor % of production in comparison to untreated PAO1
Curcumin-treated PAO1 Nano-curcumin-treated PAO1 Zein-treated PAO1
Biofilm formation 75.7 ± 4.0 29.0 ± 4.6 116 ± 4.1
Swarming motility 17.3 ± 4.2 24.3 ± 4.1 81.7 ± 4.1
Production of proteases 72.0 ± 2.6 72.3 ± 2.1 99.6 ± 4
Production of hemolysins 70.3 ± 4.5 46 ± 5.3 111 ± 4.1
Production of pyocyanin 25.7 ± 4.0 32.3 ± 2.5 99.6 ± 4.0

These results comply with other studies that showed significant anti-biofilm activities of curcumin in bulk or formulated as nanoparticles [93,94,95] against both Gram-negative and Gram-positive bacteria. For instance, Loo et al. showed that the combination of silver nanoparticles and curcumin nanoparticles at 100 μg/mL disrupted 50% of the established P. aeruginosa biofilm [94], while our zein-based nanoparticles diminished 70% biofilm formation at a concentration of 150 μg/mL. In another example, Jaiswal et al. showed that curcumin–silver nanoparticles inhibited 85% of P. aeruginosa biofilm at a concentration of 10 mg/mL [82], which is a very high concentration in comparison to our preparation. These findings underscore the considered antibiofilm efficacy of our zein-based nanoparticles at low concentrations (150 μg/mL) in comparison to other nanoparticle preparations.

3.4 Curtailing of bacterial motility

Bacterial motility is required for infection spread and establishment into the host and its inhibition could reflect effective anti-virulence activities [96,97]. Furthermore, the nonmotile mutants were unable to adhere to host tissues and form biofilms [98,99], which resulted in diminishing the bacterial capacity to induce pathogenesis [98,100]. The swarming motility of P. aeruginosa was assessed in MH agar plates provided with curcumin alone, curcumin nanoformulated, or zein at sub-MIC in comparison to untreated bacteria (Figure 3). The curcumin alone, curcumin nanoformulated, and zein significantly reduced the bacterial motility by 85, 75, and 20%, respectively. However, there was no significant difference between the effect of curcumin alone or curcumin in nanoformulation on motility; the motility was significantly reduced in plates containing curcumin as compared to plates containing zein. These findings indicate the significant effect of curcumin in inhibiting bacterial motility.

Figure 3 Curcumin reduces bacterial motility. The swarming zone of P. aeruginosa PAO1 was measured on plates provided with or without curcumin, curcumin nanoformulated, and zein at sub-MIC. However, zein significantly reduced the motility as compared to control untreated bacteria, curcumin alone, or curcumin nanoformulated and significantly reduced the motility as compared to zein-treated bacteria or untreated bacteria. There was no significant difference between the inhibitory effect of curcumin or curcumin in nanoformula on motility. Non-significant (ns): p > 0.05; ***p < 0.001.
Figure 3

Curcumin reduces bacterial motility. The swarming zone of P. aeruginosa PAO1 was measured on plates provided with or without curcumin, curcumin nanoformulated, and zein at sub-MIC. However, zein significantly reduced the motility as compared to control untreated bacteria, curcumin alone, or curcumin nanoformulated and significantly reduced the motility as compared to zein-treated bacteria or untreated bacteria. There was no significant difference between the inhibitory effect of curcumin or curcumin in nanoformula on motility. Non-significant (ns): p > 0.05; ***p < 0.001.

3.5 Reduction of production of proteases

The virulent bacteria employ diverse extracellular enzymes to establish their accommodation in the host tissue. Protease is one of the important enzymes that enables bacteria to spread and establish infections in the host tissues [101,102]. The skim milk method was used to assess the inhibitory effects on the production of protease at sub-MIC concentrations. The hydrolysis zone on the skim milk agar was measured and compared. Curcumin alone or curcumin nanoformulated significantly decreased the production of protease to about 25%. It is worth mentioning that zein does not affect the production of protease (Figure 4).

Figure 4 Curcumin decreased the production of protease. The developed hydrolysis zones around wells containing equivalent amounts of P. aeruginosa PAO1 treated with or without curcumin alone or nanoformulated, or zein at sub-MIC were measured on skim milk containing agar plates. Zein has no effect on protease production compared to control untreated bacteria, curcumin alone, or curcumin nanoformulated, and significantly reduced the protease production as compared to zein-treated bacteria or untreated bacteria. There was no significant difference between the inhibitory effect of curcumin or curcumin in nanoformula on protease production. ns: p > 0.05; ***: p < 0.001.
Figure 4

Curcumin decreased the production of protease. The developed hydrolysis zones around wells containing equivalent amounts of P. aeruginosa PAO1 treated with or without curcumin alone or nanoformulated, or zein at sub-MIC were measured on skim milk containing agar plates. Zein has no effect on protease production compared to control untreated bacteria, curcumin alone, or curcumin nanoformulated, and significantly reduced the protease production as compared to zein-treated bacteria or untreated bacteria. There was no significant difference between the inhibitory effect of curcumin or curcumin in nanoformula on protease production. ns: p > 0.05; ***: p < 0.001.

3.6 Diminishing of hemolysin activity

Among P. aeruginosa's huge arsenal of virulence factors, hemolysins play roles in the establishment of its infection and escape from the immune systems [103,104]. The effect of curcumin on the production of hemolysins was evaluated at sub-MIC. However, zein did not increase the hemolysis significantly in comparison to untreated bacteria, curcumin alone, or curcumin nanoformulated, and significantly decreased the bacterial hemolysin activity to about 30 and 50%, respectively. The nano-formulated curcumin showed a significant ability to reduce hemolysin activity in comparison to curcumin alone (Figure 5).

Figure 5 Curcumin decreased the hemolysin activity. The hemolytic activity of P. aeruginosa PAO1 was assessed in the presence of curcumin alone, curcumin nanoformulated, or zein at sub-MICs. The curcumin alone or curcumin nanoformulated significantly decreased the bacterial hemolysis activity as compared to untreated or zein-treated bacteria; however, curcumin nanoformulated significantly decreased hemolysin activity in comparison to curcumin alone. In contrast, zein increased the blood hemolysis but nonsignificantly. ns: p > 0.05; ***: p < 0.001.
Figure 5

Curcumin decreased the hemolysin activity. The hemolytic activity of P. aeruginosa PAO1 was assessed in the presence of curcumin alone, curcumin nanoformulated, or zein at sub-MICs. The curcumin alone or curcumin nanoformulated significantly decreased the bacterial hemolysis activity as compared to untreated or zein-treated bacteria; however, curcumin nanoformulated significantly decreased hemolysin activity in comparison to curcumin alone. In contrast, zein increased the blood hemolysis but nonsignificantly. ns: p > 0.05; ***: p < 0.001.

3.7 Reduction of pyocyanin production

P. aeruginosa employs a wide diverse array of virulence factors, including its greenish pigment pyocyanin, which plays an important role in its virulence [105,106]. Pyocyanin plays a role in the oxidative stress response, biofilm formation, and the virulence of P. aeruginosa in various infections [106,107]. It can also have toxic effects on host tissues and cells, making it an important factor in the study of P. aeruginosa infections and their treatment [108]. In the current study, zein did not show any effect on the pyocyanin production. Curcumin alone or curcumin nanoformulated significantly decreased the production of pyocyanin in comparison to untreated bacteria. There was no significant difference between the effect of curcumin alone or nanoformulated curcumin on pyocyanin production (Figure 6).

Figure 6 Curcumin decreased pyocyanin production. The absorbances of the pyocyanin pigment were measured in the presence of curcumin alone, curcumin nanoformulated, or zein at sub-MICs in comparison to untreated bacteria. The curcumin alone or curcumin nanoformulated significantly decreased the production of pyocyanin as compared to untreated or zein-treated bacteria. There was no significant difference between curcumin alone or curcumin nanoformulated on the pyocyanin production. ns: p > 0.05; ***p < 0.001.
Figure 6

Curcumin decreased pyocyanin production. The absorbances of the pyocyanin pigment were measured in the presence of curcumin alone, curcumin nanoformulated, or zein at sub-MICs in comparison to untreated bacteria. The curcumin alone or curcumin nanoformulated significantly decreased the production of pyocyanin as compared to untreated or zein-treated bacteria. There was no significant difference between curcumin alone or curcumin nanoformulated on the pyocyanin production. ns: p > 0.05; ***p < 0.001.

3.8 Anti-QS activities of curcumin

P. aeruginosa mainly employs three QS systems to orchestrate virulence during the different stages of infections [109]. The QS systems include two Lux-type systems, Las and Rhl and one non-Lux-type Pqs QS system [34,110]. Furthermore, there is a fourth QS system Qsc that senses the Lux-type autoinducers [111].

3.8.1 Downregulation of QS encoding genes

To investigate the anti-QS activity, the expressions of QS encoding genes were quantified in the presence of curcumin in nanoformulation (Figure 7). The results showed significant downregulation of the QS encoding genes in the presence of curcumin, which could explain the diminishing of other virulence factors that are controlled by the QS system phenotypically.

Figure 7 Curcumin downregulated the expression of QS-encoding genes. RT-PCR was employed to quantify the expression of genes that encode QS receptors and inducer synthetases in the presence or absence of curcumin nanoformulation at sub-MIC. Curcumin in nanoformula significantly downregulated the expression of all the QS-controlling genes. ***: p < 0.001.
Figure 7

Curcumin downregulated the expression of QS-encoding genes. RT-PCR was employed to quantify the expression of genes that encode QS receptors and inducer synthetases in the presence or absence of curcumin nanoformulation at sub-MIC. Curcumin in nanoformula significantly downregulated the expression of all the QS-controlling genes. ***: p < 0.001.

3.8.2 Virtual affinity of curcumin to QS receptors

To explore molecular interactions of curcumin with P. aeruginosa QS receptors, in silico docking studies were performed. The docking procedures were first validated by re-docking the co-crystallized ligand for each studied receptor. 3M5 (N-(3-oxodecanoyl)-l-homoserine lactone), EWM (N-[(3S)-2-oxooxolan-3-yl] dodecanamide), and NNQ (2-nonylquinolin-4(1H)-one) are the co-crystallized ligands for P. aeruginosa LasR, QscR, and PqsR, respectively. The root mean standard deviation (RMSD) values of re-docked 3M5, EWM, and NNQ are 1.2689, 1.4791, and 1.4520 Å, respectively, which indicate the validity of the docking procedures. Molecular docking of curcumin and the co-crystallized ligands (3M5, EWM, and NNQ) with P. aeruginosa QS receptors revealed comparable results within the active site (Table 2).

Table 2

Docking details of curcumin and reference ligands with P. aeruginosa LasR, QscR, and PqsR

Compound S score (kcal/mol) H-bond interaction Pi interaction
LasR (PDB: 6MVN)
Curcumin −7.9979 Arg61, Asp73, Leu110, Leu125 Trp88
Co-crystallized ligand: 3M5 −8.7019 Tyr56, Trp60, Asp73, Ser129 Trp88
QscR (PDB: 6CC0)
Curcumin −7.5263 Ile125 Tyr58
Co-crystallized ligand: EWM −9.8344 Tyr58, Trp62, Asp75 —
PqsR (PDB: 4JVD)
Curcumin −7.2839 — Leu208, Ile236, Tyr258
Co-crystallized ligand: NNQ −6.6745 Leu197 Leu208

Curcumin showed good binding affinity within the active site of P. aeruginosa LasR (PDB: 6MVN), where the binding energy score is −7.9979 kcal/mol. Notably, one phenolic OH group showed an H-bond interaction with Leu 110, and the second one showed an H-bond interaction with Leu 125 on the other side of the active site. One carbonyl group exhibited an H-bond interaction with the basic Arg 61. The methoxy group formed an H-bond interaction with the acidic Asp 73. Additionally, the curcumin structure was stabilized through pi–pi bond interaction with Trp 88. The curcumin structure showed hydrophobic contacts with Leu 36, Tyr 47, Tyr 64, Val 76, and Trp 88 residues (Figure 8a and b).

Curcumin was able to fill the active pocket space and showed a good binding affinity with P. aeruginosa QscR (PDB: 6CC0) with an S score of −7.5263 kcal/mol. The phenolic OH group formed an H-bond interaction with Ile 125. The phenyl ring participated in the curcumin stability through the formation of pi–H bond interaction with Tyr 58. Moreover, the curcumin structure revealed hydrophobic contacts with the following residues: Phe54, Tyr 58, Tyr 66, and Met 127 (Figure 8c and d).

Figure 8 (a) 3D curcumin–P. aeruginosa LasR (PDB: 6MVN) interaction diagram. (b) Curcumin in the molecular surface of the LasR active site. (c) 3D curcumin – P. aeruginosa QscR (PDB: 6CC0) interaction diagram. (d) Curcumin in the molecular surface of the QscR active site. (e) 3D Curcumin–P. aeruginosa pqsR (PDB: 4JVD) interaction diagram. (f) Curcumin in the molecular surface of the PqsR active site.
Figure 8

(a) 3D curcumin–P. aeruginosa LasR (PDB: 6MVN) interaction diagram. (b) Curcumin in the molecular surface of the LasR active site. (c) 3D curcumin – P. aeruginosa QscR (PDB: 6CC0) interaction diagram. (d) Curcumin in the molecular surface of the QscR active site. (e) 3D Curcumin–P. aeruginosa pqsR (PDB: 4JVD) interaction diagram. (f) Curcumin in the molecular surface of the PqsR active site.

Curcumin structure could fill the active pocket of P. aeruginosa PqsR (PDB: 4JVD) where the binding energy of curcumin is lower than that of the co-crystallized ligand (NNQ) (Table 1). On one side of the active pocket, the phenyl ring exhibited two pi–H bond interactions with Leu 208 and Ile 236 residues. The second phenyl ring, on the other side of the pocket, showed pi–pi bond interactions with Tyr 258. Besides, the curcumin structure stabilized through hydrophobic interactions with Leu 207, Leu 208, Ile 236, Tyr 258, and Ile 263 residues (Figure 8e and f).

Overall, these molecular docking studies present the potential inhibition effect of curcumin into P. aeruginosa QS receptors. The molecular interactions of curcumin with P. aeruginosa LasR (PDB: 6MVN), QscR (PDB: 6CC0), and PqsR (PDB: 4JVD) are depicted in Figure 8.

3.9 Nanoformulated curcumin-protected mice

To appraise the protective effect of curcumin nanoformula on alleviating the P. aeruginosa-induced pathogenesis, demonstrative renal and hepatic photomicrographs were taken for tissues isolated from mice intraperitoneally injected with treated or untreated bacteria (Figure 9). The liver tissues of mice infected with untreated P. aeruginosa showed severe hepatic blood vessel congestions accompanied by severe perivascular and periductal infiltration of leucocytes (Figure 9a–c). In the same way, the kidney tissues isolated from the group that was infected with untreated P. aeruginosa showed hemorrhage with interstitial edema and severe hypotrophy of renal glomeruli in the renal cortex with diffuse inflammatory cell infiltrations (Figure 9d–f). On the other hand, the liver (Figure 9g–i) and kidney (Figure 9j–l) tissues that were isolated from the group injected with treated P. aeruginosa showed no to mild congestions of blood vessels with minimal infiltrations of lymphocytes. These data show obviously the in vivo protecting effect of curcumin nanoformula against P. aeruginosa pathogenesis.

Figure 9 Histopathological examination of the isolated renal and hepatic tissues from mice groups that were infected with P. aeruginosa PAO1 or injected with P. aeruginosa PAO1 treated with curcumin nanoformula at 1/8 MIC (0.15 mg/mL). Photomicrograph of the H&E-stained liver section of the infected group showing (a) severe congestion of hepatic blood vessels (arrows head) with perivascular leucocyte cell infiltration (arrows), (b) subcapsular coagulative necrosis of hepatocytes (arrowhead) represented by nuclear pyknosis, and (c) severe focal perivascular and periductal leucocytic cell infiltration (arrow). Photomicrograph of the H&E-stained kidney section of the infected group showing (d) diffuse interstitial extravasated erythrocytes (hemorrhage) (arrows) with interstitial edema (arrowhead) and degenerated renal tubules within renal cortex, (e) severe hypotrophy of renal glomeruli in the renal cortex (arrows) with diffuse inflammatory cell infiltration (arrows head), and (f) perivascular edema (arrowhead) with endothelins and interstitial leucocytic cell infiltration cloudy swelling (arrows). Photomicrographs of the H&E-stained liver section of the infected and treated group showing (g) focal moderate perivascular areas of cellular infiltration (arrows) with mildly dilated sinusoids and macrophage infiltration (arrows head), (h) diffuse infiltration of von Kupffer cells (arrows head) with mild sinusoidal dilation (arrows), and (i) mild congestion of hepatic blood vessels (arrowhead) with mild perivascular inflammatory cell infiltration (arrow). Photomicrographs of the H&E-stained kidney section of infected and treated group showing (j) focal area of cystic dilation of some renal tubules (arrows) with normal medulla, (k) focal splitting of some renal tubules (arrows head), which appeared atrophied within the normal renal cortex, and (l) mild diffuse degeneration of renal tubules within renal medulla represented by cloudy swelling (arrows head) (scale bar = 100 µm).
Figure 9

Histopathological examination of the isolated renal and hepatic tissues from mice groups that were infected with P. aeruginosa PAO1 or injected with P. aeruginosa PAO1 treated with curcumin nanoformula at 1/8 MIC (0.15 mg/mL). Photomicrograph of the H&E-stained liver section of the infected group showing (a) severe congestion of hepatic blood vessels (arrows head) with perivascular leucocyte cell infiltration (arrows), (b) subcapsular coagulative necrosis of hepatocytes (arrowhead) represented by nuclear pyknosis, and (c) severe focal perivascular and periductal leucocytic cell infiltration (arrow). Photomicrograph of the H&E-stained kidney section of the infected group showing (d) diffuse interstitial extravasated erythrocytes (hemorrhage) (arrows) with interstitial edema (arrowhead) and degenerated renal tubules within renal cortex, (e) severe hypotrophy of renal glomeruli in the renal cortex (arrows) with diffuse inflammatory cell infiltration (arrows head), and (f) perivascular edema (arrowhead) with endothelins and interstitial leucocytic cell infiltration cloudy swelling (arrows). Photomicrographs of the H&E-stained liver section of the infected and treated group showing (g) focal moderate perivascular areas of cellular infiltration (arrows) with mildly dilated sinusoids and macrophage infiltration (arrows head), (h) diffuse infiltration of von Kupffer cells (arrows head) with mild sinusoidal dilation (arrows), and (i) mild congestion of hepatic blood vessels (arrowhead) with mild perivascular inflammatory cell infiltration (arrow). Photomicrographs of the H&E-stained kidney section of infected and treated group showing (j) focal area of cystic dilation of some renal tubules (arrows) with normal medulla, (k) focal splitting of some renal tubules (arrows head), which appeared atrophied within the normal renal cortex, and (l) mild diffuse degeneration of renal tubules within renal medulla represented by cloudy swelling (arrows head) (scale bar = 100 µm).

In a nutshell, targeting bacterial virulence is a promising strategy for controlling bacterial infections, and it offers several advantages when natural compounds are used. The effectiveness of this approach can be significantly enhanced by utilizing nanoparticle formulations. The anti-virulence and anti-QS activities of curcumin–zein nanoparticles have been evaluated in comparison to bulk curcumin. In bulk, curcumin showed a significant ability to diminish P. aeruginosa’s ability to form biofilms and produce virulence factors, such as hemolysins, proteases, and pyocyanin. However, nanoparticle formulation significantly decreased the biofilm formation and reduced the production of virulence factors at lower MIC than curcumin in bulk. Curcumin acquires significant anti-QS activities that could explain its anti-virulence activity. These anti-QS activities are attributed to the curcumin’s interference with the QS receptors besides its ability to downregulate the QS-encoding genes. Furthermore, the in vivo results emphasized the nanoparticle’s significant effects in relieving the P. aeruginosa-associated pathogenesis. Collectively, the curcumin zein nano-based formulation demonstrated effective antibacterial, anti-virulence, and antibiofilm activities against P. aeruginosa in both in vitro and in vivo studies.

Acknowledgments

This project was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Saudi Arabia, Jeddah, under grant no. (RG-17-166-43). The authors, therefore, acknowledge and thank DSR for technical and financial support.

  1. Funding information: The Deanship of Scientific Research (DSR) at King Abdulaziz University (KAU), Jeddah, Saudi Arabia, has funded this project.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Conflict of interest: The authors state no conflict of interest.

  4. Ethical approval: All in vivo procedures were carried out in strict accordance with the relevant ethical guidelines for animal welfare, as approved by the Institutional Animal Care and Use Committee at Zagazig University (ZU-IACUC), Egypt (Approval number: ZU-IACUC/3/F/154/2022).

References

[1] Carattoli A. Plasmids and the spread of resistance. Int J Med Microbiol. 2013;303(6–7):298–304.10.1016/j.ijmm.2013.02.001Search in Google Scholar PubMed

[2] Crump JA, Sjolund-Karlsson M, Gordon MA, Parry CM. Epidemiology, clinical presentation, laboratory diagnosis, antimicrobial resistance, and antimicrobial management of invasive salmonella infections. Clin Microbiol Rev. 2015;28(4):901–37.10.1128/CMR.00002-15Search in Google Scholar PubMed PubMed Central

[3] Sindeldecker D, Stoodley P. The many antibiotic resistance and tolerance strategies of Pseudomonas aeruginosa. Biofilm. 2021;3:100056.10.1016/j.bioflm.2021.100056Search in Google Scholar PubMed PubMed Central

[4] Balcazar JL, Subirats J, Borrego CM. The role of biofilms as environmental reservoirs of antibiotic resistance. Front Microbiol. 2015;6:1216.10.3389/fmicb.2015.01216Search in Google Scholar PubMed PubMed Central

[5] Hoiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O. Antibiotic resistance of bacterial biofilms. Int J Antimicrob Agents. 2010;35(4):322–32.10.1016/j.ijantimicag.2009.12.011Search in Google Scholar PubMed

[6] Crouzet M, Le Senechal C, Brozel VS, Costaglioli P, Barthe C, Bonneu M, et al. Exploring early steps in biofilm formation: set-up of an experimental system for molecular studies. BMC Microbiol. 2014;14:253.10.1186/s12866-014-0253-zSearch in Google Scholar PubMed PubMed Central

[7] Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev. 2002;15(2):167–93.10.1128/CMR.15.2.167-193.2002Search in Google Scholar PubMed PubMed Central

[8] Dheilly A, Soum-Soutera E, Klein GL, Bazire A, Compere C, Haras D, et al. Antibiofilm activity of the marine bacterium Pseudoalteromonas sp. strain 3J6. Appl Environ Microbiol. 2010;76(11):3452–61.10.1128/AEM.02632-09Search in Google Scholar PubMed PubMed Central

[9] Hoffman LR, D’Argenio DA, MacCoss MJ, Zhang Z, Jones RA, Miller SI. Aminoglycoside antibiotics induce bacterial biofilm formation. Nature. 2005;436(7054):1171–5.10.1038/nature03912Search in Google Scholar PubMed

[10] Cavalu S, Elbaramawi SS, Eissa AG, Radwan MF, S, Ibrahim T, Khafagy E-S, et al. Characterization of the anti-biofilm and anti-quorum sensing activities of the &beta;-adrenoreceptor antagonist atenolol against gram-negative bacterial pathogens. Int J Mol Sci. 2022;23(21):13088.10.3390/ijms232113088Search in Google Scholar PubMed PubMed Central

[11] Lila ASA, Rajab AA, Abdallah MH, Rizvi SMD, Moin A, Khafagy E-S, et al. Biofilm lifestyle in recurrent urinary tract infections. Life. 2023;13(1):148.10.3390/life13010148Search in Google Scholar PubMed PubMed Central

[12] Hegazy WAH, Abbas HA. Evaluation of the role of SsaV ‘Salmonella pathogenicity island-2 dependent type III secretion system components on the virulence behavior of Salmonella enterica serovar typhimurium. Afr J Biotechnol. 2017;16(14):718–26.10.5897/AJB2016.15852Search in Google Scholar

[13] Elfaky MA, Elbaramawi SS, Eissa AG, Ibrahim TS, Khafagy ES, Ali MAM, et al. Drug repositioning: doxazosin attenuates the virulence factors and biofilm formation in Gram-negative bacteria. Appl Microbiol Biotechnol. 2023;107(11):3763–78.10.1007/s00253-023-12522-3Search in Google Scholar PubMed

[14] Lim SM, Webb SA. Nosocomial bacterial infections in Intensive Care Units. I: Organisms and mechanisms of antibiotic resistance. Anaesthesia. 2005;60(9):887–902.10.1111/j.1365-2044.2005.04220.xSearch in Google Scholar PubMed

[15] Askoura M, Almalki AJ, Lila ASA, Almansour K, Alshammari F, Khafagy E-S, et al. Alteration of Salmonella enterica virulence and host pathogenesis through targeting sdiA by using the CRISPR-Cas9 system. Microorganisms. 2021;9(12):2564.10.3390/microorganisms9122564Search in Google Scholar PubMed PubMed Central

[16] Agha KA, Abo-Dya NE, Ibrahim TS, Abdel-Aal EH, Hegazy WA. Benzotriazole-mediated synthesis and antibacterial activity of novel N-acylcephalexins. Sci Pharm. 2016;84(3):484–96.10.3390/scipharm84030484Search in Google Scholar PubMed PubMed Central

[17] Gaynes R, Edwards JR. National nosocomial infections surveillance S. overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis: an official publication of the Infectious Diseases Society of America. 2005;41(6):848–54.10.1086/432803Search in Google Scholar PubMed

[18] Gogoi M, Sharma A, Hazarika NK. Biofilm formation by bacterial isolates from patients on indwelling medical devices. Indian J Med Microbiol. 2015;33(2):319–20.10.4103/0255-0857.154896Search in Google Scholar PubMed

[19] Brackman G, Cos P, Maes L, Nelis HJ, Coenye T. Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics in vitro and in vivo. Antimicrob Agents Chemother. 2011;55(6):2655–61.10.1128/AAC.00045-11Search in Google Scholar PubMed PubMed Central

[20] Rajab AA, Hegazy WA. What’s old is new again: Insights into diabetic foot microbiome. World J Diabetes. 2023;14(6):680–704.10.4239/wjd.v14.i6.680Search in Google Scholar PubMed PubMed Central

[21] Papenfort K, Bassler BL. Quorum sensing signal-response systems in Gram-negative bacteria. Nat Rev Microbiol. 2016;14(9):576–88.10.1038/nrmicro.2016.89Search in Google Scholar PubMed PubMed Central

[22] Almalki AJ, Ibrahim TS, Taher ES, Mohamed MFA, Youns M, Hegazy WAH, et al. Synthesis, antimicrobial, anti-virulence and anticancer evaluation of New 5(4H)-oxazolone-based sulfonamides. Molecules. 2022;27(3):671.10.3390/molecules27030671Search in Google Scholar PubMed PubMed Central

[23] Withers H, Swift S, Williams P. Quorum sensing as an integral component of gene regulatory networks in Gram-negative bacteria. Curr Opin Microbiol. 2001;4(2):186–93.10.1016/S1369-5274(00)00187-9Search in Google Scholar

[24] Almalki AJ, Ibrahim TS, Elhady SS, Darwish KM, Hegazy WAH. Repurposing &alpha;-adrenoreceptor blockers as promising anti-virulence agents in gram-negative bacteria. Antibiotics. 2022;11(2):178.10.3390/antibiotics11020178Search in Google Scholar PubMed PubMed Central

[25] Parsek MR, Val DL, Hanzelka BL, Cronan JE, Jr, Greenberg EP. Acyl homoserine-lactone quorum-sensing signal generation. Proc Natl Acad Sci U S A. 1999;96(8):4360–5.10.1073/pnas.96.8.4360Search in Google Scholar PubMed PubMed Central

[26] Solano C, Echeverz M, Lasa I. Biofilm dispersion and quorum sensing. Curr Opin Microbiol. 2014;18:96–104.10.1016/j.mib.2014.02.008Search in Google Scholar PubMed

[27] Elfaky MA, Thabit AK, Eljaaly K, Zawawi A, Abdelkhalek AS, Almalki AJ, et al. Controlling of bacterial virulence: Evaluation of anti-virulence activities of prazosin against Salmonella enterica. Antibiotics (Basel). 2022;11(11):1585.10.3390/antibiotics11111585Search in Google Scholar PubMed PubMed Central

[28] Sadikot RT, Blackwell TS, Christman JW, Prince AS. Pathogen–host interactions in Pseudomonas aeruginosa pneumonia. Am J Respir Crit Care Med. 2005;171(11):1209–23.10.1164/rccm.200408-1044SOSearch in Google Scholar PubMed PubMed Central

[29] Vidaillac C, Chotirmall SH. Pseudomonas aeruginosa in bronchiectasis: infection, inflammation, and therapies. Expert Rev Respir Med. 2021;15(5):649–62.10.1080/17476348.2021.1906225Search in Google Scholar PubMed

[30] Daneshvar Alavi HE, Truelstrup Hansen L. Kinetics of biofilm formation and desiccation survival of Listeria monocytogenes in single and dual species biofilms with Pseudomonas fluorescens, Serratia proteamaculans or Shewanella baltica on food-grade stainless steel surfaces. Biofouling. 2013;29(10):1253–68.10.1080/08927014.2013.835805Search in Google Scholar PubMed

[31] Denton M, Kerr K, Mooney L, Keer V, Rajgopal A, Brownlee K, et al. Transmission of colistin-resistant Pseudomonas aeruginosa between patients attending a pediatric cystic fibrosis center. Pediatr Pulmonol. 2002;34(4):257–61.10.1002/ppul.10166Search in Google Scholar PubMed

[32] Francis VI, Stevenson EC, Porter SL. Two-component systems required for virulence in Pseudomonas aeruginosa. FEMS Microbiol Lett. 2017;364(11):104.10.1093/femsle/fnx104Search in Google Scholar PubMed PubMed Central

[33] Gellatly SL, Hancock RE. Pseudomonas aeruginosa: new insights into pathogenesis and host defenses. Pathog Dis. 2013;67(3):159–73.10.1111/2049-632X.12033Search in Google Scholar PubMed

[34] Venturi V. Regulation of quorum sensing in Pseudomonas. FEMS Microbiol Rev. 2006;30(2):274–91.10.1111/j.1574-6976.2005.00012.xSearch in Google Scholar PubMed

[35] Xiao G, He J, Rahme LG. Mutation analysis of the Pseudomonas aeruginosa mvfR and pqsABCDE gene promoters demonstrates complex quorum-sensing circuitry. Microbiology (Reading). 2006;152(Pt 6):1679–86.10.1099/mic.0.28605-0Search in Google Scholar PubMed

[36] Smith RS, Iglewski BH. P. aeruginosa quorum-sensing systems and virulence. Curr Opin Microbiol. 2003;6(1):56–60.10.1016/S1369-5274(03)00008-0Search in Google Scholar PubMed

[37] Chen G, Swem LR, Swem DL, Stauff DL, O’Loughlin CT, Jeffrey PD, et al. A strategy for antagonizing quorum sensing. Mol Cell. 2011;42(2):199–209.10.1016/j.molcel.2011.04.003Search in Google Scholar PubMed PubMed Central

[38] Ma Y, Wang Y-R, He Y-H, Ding Y-Y, An J-X, Zhang Z-J, et al. Drug repurposing strategy part 1: from approved drugs to agri-bactericides leads. J Antibiotics. 2023;76(1):27–51.10.1038/s41429-022-00574-ySearch in Google Scholar PubMed PubMed Central

[39] Rasko DA, Sperandio V. Anti-virulence strategies to combat bacteria-mediated disease. Nat Rev Drug Discov. 2010;9(2):117–28.10.1038/nrd3013Search in Google Scholar PubMed

[40] Khayat MT, Abbas HA, Ibrahim TS, Elbaramawi SS, Khayyat AN, Alharbi M, et al. Synergistic benefits: exploring the anti-virulence effects of metformin/vildagliptin antidiabetic combination against Pseudomonas aeruginosa via controlling quorum sensing systems. Biomedicines. 2023;11(5):1442.10.3390/biomedicines11051442Search in Google Scholar PubMed PubMed Central

[41] Khayat MT, Abbas HA, Ibrahim TS, Khayyat AN, Alharbi M, Darwish KM, et al. Anti-quorum sensing activities of gliptins against pseudomonas aeruginosa and staphylococcus aureus. Biomedicines. 2022;10(5):1169.10.3390/biomedicines10051169Search in Google Scholar PubMed PubMed Central

[42] Khayat MT, Elbaramawi SS, Nazeih SI, Safo MK, Khafagy E-S, Ali MA, et al. Diminishing the pathogenesis of the food-borne pathogen serratia marcescens by low doses of sodium citrate. Biology. 2023;12(4):504.10.3390/biology12040504Search in Google Scholar PubMed PubMed Central

[43] Khayat MT, Ibrahim TS, Darwish KM, Khayyat AN, Alharbi M, Khafagy ES, et al. Hiring of the anti-quorum sensing activities of hypoglycemic agent linagliptin to alleviate the pseudomonas aeruginosa pathogenesis. Microorganisms. 2022;10(12):2455.10.3390/microorganisms10122455Search in Google Scholar PubMed PubMed Central

[44] Garcia-Contreras R. Is quorum sensing interference a viable alternative to treat pseudomonas aeruginosa infections? Front Microbiol. 2016;7:1454.10.3389/fmicb.2016.01454Search in Google Scholar PubMed PubMed Central

[45] Jiang Q, Chen J, Yang C, Yin Y, Yao K. Quorum sensing: a prospective therapeutic target for bacterial diseases. BioMed Res Int. 2019;2019:2015978.10.1155/2019/2015978Search in Google Scholar PubMed PubMed Central

[46] Hegazy WAH, Khayat MT, Ibrahim TS, Youns M, Mosbah R, Soliman WE. Repurposing of antidiabetics as Serratia marcescens virulence inhibitors. Braz J Microbiol. 2021;52(2):627–38.10.1007/s42770-021-00465-8Search in Google Scholar PubMed PubMed Central

[47] Khayyat AN, Hegazy WAH, Shaldam MA, Mosbah R, Almalki AJ, Ibrahim TS, et al. Xylitol inhibits growth and blocks virulence in serratia marcescens. Microorganisms. 2021;9(5):1083.10.3390/microorganisms9051083Search in Google Scholar PubMed PubMed Central

[48] Youns M, Askoura M, Abbas HA, Attia GH, Khayyat AN, Goda RM, et al. Celastrol modulates multiple signaling pathways to inhibit proliferation of PANCREATIC cancer via DDIT3 and ATF3 Up-regulation and RRM2 and MCM4 down-regulation. Onco Targets Ther. 2021;14:3849–60.10.2147/OTT.S313933Search in Google Scholar PubMed PubMed Central

[49] Khayat MT, Ibrahim TS, Khayyat AN, Alharbi M, Shaldam MA, Mohammad KA, et al. Sodium citrate alleviates virulence in pseudomonas aeruginosa. Microorganisms. 2022;10(5):1046.10.3390/microorganisms10051046Search in Google Scholar PubMed PubMed Central

[50] Aldawsari MF, Khafagy ES, Saqr AA, Alalaiwe A, Abbas HA, Shaldam MA, et al. Tackling virulence of pseudomonas aeruginosa by the natural furanone sotolon. Antibiotics (Basel). 2021;10(7):871.10.3390/antibiotics10070871Search in Google Scholar PubMed PubMed Central

[51] Singh R, Chauhan N, Kuddus M. Exploring the therapeutic potential of marine-derived bioactive compounds against COVID-19. Environ Sci Pollut Res. 2021;28(38):52798–809.10.1007/s11356-021-16104-6Search in Google Scholar PubMed PubMed Central

[52] Teow S-Y, Liew K, Ali SA, Khoo AS-B, Peh S-C. Antibacterial action of curcumin against Staphylococcus aureus: a brief review. J Trop Med. 2016;2016:1–10.10.1155/2016/2853045Search in Google Scholar PubMed PubMed Central

[53] Gunes H, Gulen D, Mutlu R, Gumus A, Tas T, Topkaya AE. Antibacterial effects of curcumin: an in vitro minimum inhibitory concentration study. Toxicol Ind Health. 2016;32(2):246–50.10.1177/0748233713498458Search in Google Scholar PubMed

[54] Lestari ML, Indrayanto G. Curcumin. Profiles Drug Subst Excip Relat Methodol. 2014;39:113–204.10.1016/B978-0-12-800173-8.00003-9Search in Google Scholar PubMed

[55] Sharma R, Gescher A, Steward W. Curcumin: the story so far. Eur J Cancer. 2005;41(13):1955–68.10.1016/j.ejca.2005.05.009Search in Google Scholar PubMed

[56] Alandiyjany MN, Abdelaziz AS, Abdelfattah-Hassan A, Hegazy WAH, Hassan AA, Elazab ST, et al. Novel in vivo assessment of antimicrobial efficacy of ciprofloxacin loaded mesoporous silica nanoparticles against salmonella typhimurium infection. Pharmaceuticals. 2022;15(3):357.10.3390/ph15030357Search in Google Scholar PubMed PubMed Central

[57] Alshahrani SM, Khafagy ES, Riadi Y, Al Saqr A, Alfadhel MM, Hegazy WAH. Amphotericin B-PEG Conjugates of ZnO nanoparticles: Enhancement antifungal activity with minimal toxicity. Pharmaceutics. 2022;14(8):1646.10.3390/pharmaceutics14081646Search in Google Scholar PubMed PubMed Central

[58] Zheng D, Huang C, Huang H, Zhao Y, Khan MRU, Zhao H, et al. Antibacterial mechanism of curcumin: A review. Chem Biodiversity. 2020;17(8):e2000171.10.1002/cbdv.202000171Search in Google Scholar PubMed

[59] Perera W, Dissanayake RK, Ranatunga U, Hettiarachchi N, Perera K, Unagolla JM, et al. Curcumin loaded zinc oxide nanoparticles for activity-enhanced antibacterial and anticancer applications. RSC Adv. 2020;10(51):30785–95.10.1039/D0RA05755JSearch in Google Scholar PubMed PubMed Central

[60] Algandaby MM, Al-Sawahli MM, Ahmed OA, Fahmy UA, Abdallah HM, Hattori M, et al. Curcumin-zein nanospheres improve liver targeting and antifibrotic activity of curcumin in carbon tetrachloride-induced mice liver fibrosis. J Biomed Nanotechnol. 2016;12(9):1746–57.10.1166/jbn.2016.2270Search in Google Scholar PubMed

[61] Khayyat AN, Abbas HA, Khayat MT, Shaldam MA, Askoura M, Asfour HZ, et al. Secnidazole is a promising imidazole mitigator of serratia marcescens virulence. Microorganisms. 2021;9(11):2333.10.3390/microorganisms9112333Search in Google Scholar PubMed PubMed Central

[62] Thabit AK, Eljaaly K, Zawawi A, Ibrahim TS, Eissa AG, Elbaramawi SS, et al. Muting bacterial communication: evaluation of prazosin anti-quorum sensing activities against gram-negative bacteria pseudomonas aeruginosa, proteus mirabilis, and serratia marcescens. Biology (Basel). 2022;11(9):1349.10.3390/biology11091349Search in Google Scholar PubMed PubMed Central

[63] Thabit AK, Eljaaly K, Zawawi A, Ibrahim TS, Eissa AG, Elbaramawi SS, et al. Silencing of salmonella typhimurium pathogenesis: atenolol acquires efficient anti-virulence activities. Microorganisms. 2022;10(10):1976.10.3390/microorganisms10101976Search in Google Scholar PubMed PubMed Central

[64] Hegazy WAH, Salem IM, Alotaibi HF, Khafagy E-S, Ibrahim D. Terazosin interferes with quorum sensing and type three secretion system and diminishes the bacterial espionage to mitigate the salmonella typhimurium pathogenesis. Antibiotics. 2022;11(4):465.10.3390/antibiotics11040465Search in Google Scholar PubMed PubMed Central

[65] Askoura M, Abbas HA, Al Sadoun H, Abdulaal WH, Abu Lila AS, Almansour K, et al. Elevated levels of IL-33, IL-17 and IL-25 Indicate the progression from chronicity to hepatocellular carcinoma in hepatitis C virus patients. Pathogens. 2022;11(1):57.10.3390/pathogens11010057Search in Google Scholar PubMed PubMed Central

[66] Alotaibi HF, Alotaibi H, Darwish KM, Khafagy E-S, Abu Lila AS, Ali MA, et al. The anti-virulence activities of the antihypertensive drug propranolol in light of its anti-quorum sensing effects against pseudomonas aeruginosa and serratia marcescens. Biomedicines. 2023;11(12):3161.10.3390/biomedicines11123161Search in Google Scholar PubMed PubMed Central

[67] Hegazy WAH. Hepatitis C virus pathogenesis: Serum IL-33 level indicates liver damage. Afr J Microbiol Res. 2015;9(20):1386–93.10.5897/AJMR2015.7496Search in Google Scholar

[68] McCready AR, Paczkowski JE, Henke BR, Bassler BL. Structural determinants driving homoserine lactone ligand selection in the Pseudomonas aeruginosa LasR quorum-sensing receptor. Proc Natl Acad Sci. 2019;116(1):245–54.10.1073/pnas.1817239116Search in Google Scholar PubMed PubMed Central

[69] Wysoczynski‐Horita CL, Boursier ME, Hill R, Hansen K, Blackwell HE, Churchill ME. Mechanism of agonism and antagonism of the Pseudomonas aeruginosa quorum sensing regulator QscR with non‐native ligands. Mol Microbiol. 2018;108(3):240–57.10.1111/mmi.13930Search in Google Scholar PubMed PubMed Central

[70] Ilangovan A, Fletcher M, Rampioni G, Pustelny C, Rumbaugh K, Heeb S, et al. Structural basis for native agonist and synthetic inhibitor recognition by the Pseudomonas aeruginosa quorum sensing regulator PqsR (MvfR). PLoS Pathog. 2013;9(7):e1003508.10.1371/journal.ppat.1003508Search in Google Scholar PubMed PubMed Central

[71] Nazeih SI, Ali MA, Halim ASA, Al-Lawati H, Abbas HA, Al-Zharani M, et al. Relocating glyceryl trinitrate as an anti-virulence agent against pseudomonas aeruginosa and serratia marcescens: insights from molecular and in vivo investigations. Microorganisms. 2023;11(10):2420.10.3390/microorganisms11102420Search in Google Scholar PubMed PubMed Central

[72] Herdiana Y, Wathoni N, Shamsuddin S, Muchtaridi M. Scale-up polymeric-based nanoparticles drug delivery systems: Development and challenges. OpenNano. 2022;7:100048.10.1016/j.onano.2022.100048Search in Google Scholar

[73] Rizvi SA, Saleh AM. Applications of nanoparticle systems in drug delivery technology. Saudi Pharm J. 2018;26(1):64–70.10.1016/j.jsps.2017.10.012Search in Google Scholar PubMed PubMed Central

[74] Raghunath A, Perumal E. Metal oxide nanoparticles as antimicrobial agents: a promise for the future. Int J Antimicrob Agents. 2017;49(2):137–52.10.1016/j.ijantimicag.2016.11.011Search in Google Scholar PubMed

[75] Nel A, Xia T, Madler L, Li N. Toxic potential of materials at the nanolevel. Science. 2006;311(5761):622–7.10.1126/science.1114397Search in Google Scholar PubMed

[76] Bhattacharya R, Mukherjee P. Biological properties of “naked” metal nanoparticles. Adv Drug Delivery Rev. 2008;60(11):1289–306.10.1016/j.addr.2008.03.013Search in Google Scholar PubMed

[77] Seil JT, Webster TJ. Antimicrobial applications of nanotechnology: methods and literature. Int J Nanomed. 2012;6:2767–81.10.2147/IJN.S24805Search in Google Scholar PubMed PubMed Central

[78] Binks BP, Liu W, Rodrigues JA. Novel stabilization of emulsions via the heteroaggregation of nanoparticles. Langmuir. 2008;24(9):4443–6.10.1021/la800084dSearch in Google Scholar PubMed

[79] Gupta A, Eral HB, Hatton TA, Doyle PS. Nanoemulsions: formation, properties and applications. Soft Matter. 2016;12(11):2826–41.10.1039/C5SM02958ASearch in Google Scholar

[80] Dobrovolskaia MA, McNeil SE. Immunological properties of engineered nanomaterials. Nature Nanotechnol. 2007;2(8):469–78.10.1038/nnano.2007.223Search in Google Scholar PubMed

[81] Albanese A, Tang PS, Chan WC. The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu Rev Bio Eng. 2012;14:1–16.10.1146/annurev-bioeng-071811-150124Search in Google Scholar PubMed

[82] Jaiswal S, Mishra P. Antimicrobial and antibiofilm activity of curcumin-silver nanoparticles with improved stability and selective toxicity to bacteria over mammalian cells. Medical Microbiol Immunol. 2018;207:39–53.10.1007/s00430-017-0525-ySearch in Google Scholar PubMed

[83] Kalia VC, Purohit HJ. Quenching the quorum sensing system: potential antibacterial drug targets. Critical Rev Microbiol. 2011;37(2):121–40.10.3109/1040841X.2010.532479Search in Google Scholar PubMed

[84] Rutherford ST, Bassler BL. Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harb Perspect Med. 2012;2(11):a012427.10.1101/cshperspect.a012427Search in Google Scholar PubMed PubMed Central

[85] Vestby LK, Gronseth T, Simm R, Nesse LL. Bacterial biofilm and its role in the pathogenesis of disease. Antibiotics (Basel). 2020;9(2):59.10.3390/antibiotics9020059Search in Google Scholar PubMed PubMed Central

[86] Uruen C, Chopo-Escuin G, Tommassen J, Mainar-Jaime RC, Arenas J. Biofilms as promoters of bacterial antibiotic resistance and tolerance. Antibiotics (Basel). 2020;10(1):3.10.3390/antibiotics10010003Search in Google Scholar PubMed PubMed Central

[87] Wolska KI, Grudniak AM, Rudnicka Z, Markowska K. Genetic control of bacterial biofilms. J Appl Gene. 2016;57(2):225–38.10.1007/s13353-015-0309-2Search in Google Scholar PubMed PubMed Central

[88] Sahli C, Moya SE, Lomas JS, Gravier-Pelletier C, Briandet R, Hémadi M. Recent advances in nanotechnology for eradicating bacterial biofilm. Theranostics. 2022;12(5):2383.10.7150/thno.67296Search in Google Scholar PubMed PubMed Central

[89] Ikuma K, Decho AW, Lau BL. When nanoparticles meet biofilms – interactions guiding the environmental fate and accumulation of nanoparticles. Front Microbiol. 2015;6:591.10.3389/fmicb.2015.00591Search in Google Scholar PubMed PubMed Central

[90] Qayyum S, Khan AU. Nanoparticles vs biofilms: a battle against another paradigm of antibiotic resistance. MedChemComm. 2016;7(8):1479–98.10.1039/C6MD00124FSearch in Google Scholar

[91] Tanzil AH, Sultana ST, Saunders SR, Shi L, Marsili E, Beyenal H. Biological synthesis of nanoparticles in biofilms. Enzyme Microb Technol. 2016;95:4–12.10.1016/j.enzmictec.2016.07.015Search in Google Scholar PubMed

[92] Habimana O, Steenkeste K, Fontaine-Aupart M-P, Bellon-Fontaine M-N, Kulakauskas S, Briandet R. Diffusion of nanoparticles in biofilms is altered by bacterial cell wall hydrophobicity. Appl Environ Microbiol. 2011;77(1):367–8.10.1128/AEM.02163-10Search in Google Scholar PubMed PubMed Central

[93] Vaughn AR, Haas KN, Burney W, Andersen E, Clark AK, Crawford R, et al. Potential role of curcumin against biofilm‐producing organisms on the skin: A review. Phytother Res. 2017;31(12):1807–16.10.1002/ptr.5912Search in Google Scholar PubMed

[94] Loo C-Y, Rohanizadeh R, Young PM, Traini D, Cavaliere R, Whitchurch CB, et al. Combination of silver nanoparticles and curcumin nanoparticles for enhanced anti-biofilm activities. J Agric Food Chem. 2016;64(12):2513–22.10.1021/acs.jafc.5b04559Search in Google Scholar PubMed

[95] Hu P, Huang P, Chen MW. Curcumin reduces Streptococcus mutans biofilm formation by inhibiting sortase A activity. Arch Oral Biol. 2013;58(10):1343–8.10.1016/j.archoralbio.2013.05.004Search in Google Scholar PubMed

[96] Ang S, Horng YT, Shu JC, Soo PC, Liu JH, Yi WC, et al. The role of RsmA in the regulation of swarming motility in Serratia marcescens. J Biomed Sci. 2001;8(2):160–9.10.1007/BF02256408Search in Google Scholar PubMed

[97] Kearns DB. A field guide to bacterial swarming motility. Nature Rev Microbiol. 2010;8(9):634–44.10.1038/nrmicro2405Search in Google Scholar PubMed PubMed Central

[98] de la Fuente-Nunez C, Korolik V, Bains M, Nguyen U, Breidenstein EB, Horsman S, et al. Inhibition of bacterial biofilm formation and swarming motility by a small synthetic cationic peptide. Antimicrob Agents Chemother. 2012;56(5):2696–704.10.1128/AAC.00064-12Search in Google Scholar PubMed PubMed Central

[99] Tuson HH, Copeland MF, Carey S, Sacotte R, Weibel DB. Flagellum density regulates Proteus mirabilis swarmer cell motility in viscous environments. J Bacteriol. 2013;195(2):368–77.10.1128/JB.01537-12Search in Google Scholar PubMed PubMed Central

[100] Khayyat AN, Abbas HA, Mohamed MFA, Asfour HZ, Khayat MT, Ibrahim TS, et al. Not only antimicrobial: metronidazole mitigates the virulence of proteus mirabilis isolated from macerated diabetic foot ulcer. Appl Sci. 2021;11(15):6847.10.3390/app11156847Search in Google Scholar

[101] Hangler M, Burmolle M, Schneider I, Allermann K, Jensen B. The serine protease esperase HPF inhibits the formation of multispecies biofilm. Biofouling. 2009;25(7):667–74.10.1080/08927010903096008Search in Google Scholar PubMed

[102] Voynow JA, Fischer BM, Zheng S. Proteases and cystic fibrosis. Int J Biochem Cell Biol. 2008;40(6–7):1238–45.10.1016/j.biocel.2008.03.003Search in Google Scholar PubMed PubMed Central

[103] Fernandez-Vazquez J, Cabrer-Panes JD, Aberg A, Juarez A, Madrid C, Gaviria-Cantin T, et al. ppGpp, the general stress response alarmone, is required for the expression of the alpha-hemolysin toxin in the uropathogenic escherichia coli isolate. Int J Mol Sci. 2022;23(20):J96.10.3390/ijms232012256Search in Google Scholar PubMed PubMed Central

[104] Fishman MR, Giglio K, Fay D, Filiatrault MJ. Physiological and genetic characterization of calcium phosphate precipitation by pseudomonas species. Sci Rep. 2018;8(1):10156.10.1038/s41598-018-28525-4Search in Google Scholar PubMed PubMed Central

[105] Hall S, McDermott C, Anoopkumar-Dukie S, McFarland AJ, Forbes A, Perkins AV, et al. Cellular effects of pyocyanin, a secreted virulence factor of pseudomonas aeruginosa. Toxins (Basel). 2016;8(8):236.10.3390/toxins8080236Search in Google Scholar PubMed PubMed Central

[106] Jayaseelan S, Ramaswamy D, Dharmaraj S. Pyocyanin: production, applications, challenges and new insights. World J Microbiol Biotechnol. 2014;30:1159–68.10.1007/s11274-013-1552-5Search in Google Scholar PubMed

[107] Alatraktchi FA, Svendsen WE, Molin S. Electrochemical detection of pyocyanin as a biomarker for Pseudomonas aeruginosa: A focused review. Sensors. 2020;20(18):5218.10.3390/s20185218Search in Google Scholar PubMed PubMed Central

[108] Mavrodi DV, Bonsall RF, Delaney SM, Soule MJ, Phillips G, Thomashow LS. Functional analysis of genes for biosynthesis of pyocyanin and phenazine-1-carboxamide from Pseudomonas aeruginosa PAO1. J Bacteriol. 2001;183(21):6454–65.10.1128/JB.183.21.6454-6465.2001Search in Google Scholar PubMed PubMed Central

[109] Juhas M, Eberl L, Tummler B. Quorum sensing: the power of cooperation in the world of Pseudomonas. Environ Microbiol. 2005;7(4):459–71.10.1111/j.1462-2920.2005.00769.xSearch in Google Scholar PubMed

[110] Nalca Y, Jansch L, Bredenbruch F, Geffers R, Buer J, Haussler S. Quorum-sensing antagonistic activities of azithromycin in pseudomonas aeruginosa PAO1: a global approach. Antimicrob Agents Chemother. 2006;50(5):1680–8.10.1128/AAC.50.5.1680-1688.2006Search in Google Scholar PubMed PubMed Central

[111] Lintz MJ, Oinuma K, Wysoczynski CL, Greenberg EP, Churchill ME. Crystal structure of QscR, a Pseudomonas aeruginosa quorum sensing signal receptor. Proc Natl Acad Sci U S A. 2011;108(38):15763–8.10.1073/pnas.1112398108Search in Google Scholar PubMed PubMed Central

Received: 2023-10-22
Revised: 2024-01-02
Accepted: 2024-02-04
Published Online: 2024-03-11

© 2024 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

  1. Research Articles
  2. Tension buckling and postbuckling of nanocomposite laminated plates with in-plane negative Poisson’s ratio
  3. Polyvinylpyrrolidone-stabilised gold nanoparticle coatings inhibit blood protein adsorption
  4. Energy and mass transmission through hybrid nanofluid flow passing over a spinning sphere with magnetic effect and heat source/sink
  5. Surface treatment with nano-silica and magnesium potassium phosphate cement co-action for enhancing recycled aggregate concrete
  6. Numerical investigation of thermal radiation with entropy generation effects in hybrid nanofluid flow over a shrinking/stretching sheet
  7. Enhancing the performance of thermal energy storage by adding nano-particles with paraffin phase change materials
  8. Using nano-CaCO3 and ceramic tile waste to design low-carbon ultra high performance concrete
  9. Numerical analysis of thermophoretic particle deposition in a magneto-Marangoni convective dusty tangent hyperbolic nanofluid flow – Thermal and magnetic features
  10. Dual numerical solutions of Casson SA–hybrid nanofluid toward a stagnation point flow over stretching/shrinking cylinder
  11. Single flake homo p–n diode of MoTe2 enabled by oxygen plasma doping
  12. Electrostatic self-assembly effect of Fe3O4 nanoparticles on performance of carbon nanotubes in cement-based materials
  13. Multi-scale alignment to buried atom-scale devices using Kelvin probe force microscopy
  14. Antibacterial, mechanical, and dielectric properties of hydroxyapatite cordierite/zirconia porous nanocomposites for use in bone tissue engineering applications
  15. Time-dependent Darcy–Forchheimer flow of Casson hybrid nanofluid comprising the CNTs through a Riga plate with nonlinear thermal radiation and viscous dissipation
  16. Durability prediction of geopolymer mortar reinforced with nanoparticles and PVA fiber using particle swarm optimized BP neural network
  17. Utilization of zein nano-based system for promoting antibiofilm and anti-virulence activities of curcumin against Pseudomonas aeruginosa
  18. Antibacterial effect of novel dental resin composites containing rod-like zinc oxide
  19. An extended model to assess Jeffery–Hamel blood flow through arteries with iron-oxide (Fe2O3) nanoparticles and melting effects: Entropy optimization analysis
  20. Comparative study of copper nanoparticles over radially stretching sheet with water and silicone oil
  21. Cementitious composites modified by nanocarbon fillers with cooperation effect possessing excellent self-sensing properties
  22. Confinement size effect on dielectric properties, antimicrobial activity, and recycling of TiO2 quantum dots via photodegradation processes of Congo red dye and real industrial textile wastewater
  23. Biogenic silver nanoparticles of Moringa oleifera leaf extract: Characterization and photocatalytic application
  24. Novel integrated structure and function of Mg–Gd neutron shielding materials
  25. Impact of multiple slips on thermally radiative peristaltic transport of Sisko nanofluid with double diffusion convection, viscous dissipation, and induced magnetic field
  26. Magnetized water-based hybrid nanofluid flow over an exponentially stretching sheet with thermal convective and mass flux conditions: HAM solution
  27. A numerical investigation of the two-dimensional magnetohydrodynamic water-based hybrid nanofluid flow composed of Fe3O4 and Au nanoparticles over a heated surface
  28. Development and modeling of an ultra-robust TPU-MWCNT foam with high flexibility and compressibility
  29. Effects of nanofillers on the physical, mechanical, and tribological behavior of carbon/kenaf fiber–reinforced phenolic composites
  30. Polymer nanocomposite for protecting photovoltaic cells from solar ultraviolet in space
  31. Study on the mechanical properties and microstructure of recycled concrete reinforced with basalt fibers and nano-silica in early low-temperature environments
  32. Synergistic effect of carbon nanotubes and polyvinyl alcohol on the mechanical performance and microstructure of cement mortar
  33. CFD analysis of paraffin-based hybrid (Co–Au) and trihybrid (Co–Au–ZrO2) nanofluid flow through a porous medium
  34. Forced convective tangent hyperbolic nanofluid flow subject to heat source/sink and Lorentz force over a permeable wedge: Numerical exploration
  35. Physiochemical and electrical activities of nano copper oxides synthesised via hydrothermal method utilising natural reduction agents for solar cell application
  36. A homotopic analysis of the blood-based bioconvection Carreau–Yasuda hybrid nanofluid flow over a stretching sheet with convective conditions
  37. In situ synthesis of reduced graphene oxide/SnIn4S8 nanocomposites with enhanced photocatalytic performance for pollutant degradation
  38. A coarse-grained Poisson–Nernst–Planck model for polyelectrolyte-modified nanofluidic diodes
  39. A numerical investigation of the magnetized water-based hybrid nanofluid flow over an extending sheet with a convective condition: Active and passive controls of nanoparticles
  40. The LyP-1 cyclic peptide modified mesoporous polydopamine nanospheres for targeted delivery of triptolide regulate the macrophage repolarization in atherosclerosis
  41. Synergistic effect of hydroxyapatite-magnetite nanocomposites in magnetic hyperthermia for bone cancer treatment
  42. The significance of quadratic thermal radiative scrutinization of a nanofluid flow across a microchannel with thermophoretic particle deposition effects
  43. Ferromagnetic effect on Casson nanofluid flow and transport phenomena across a bi-directional Riga sensor device: Darcy–Forchheimer model
  44. Performance of carbon nanomaterials incorporated with concrete exposed to high temperature
  45. Multicriteria-based optimization of roller compacted concrete pavement containing crumb rubber and nano-silica
  46. Revisiting hydrotalcite synthesis: Efficient combined mechanochemical/coprecipitation synthesis to design advanced tunable basic catalysts
  47. Exploration of irreversibility process and thermal energy of a tetra hybrid radiative binary nanofluid focusing on solar implementations
  48. Effect of graphene oxide on the properties of ternary limestone clay cement paste
  49. Improved mechanical properties of graphene-modified basalt fibre–epoxy composites
  50. Sodium titanate nanostructured modified by green synthesis of iron oxide for highly efficient photodegradation of dye contaminants
  51. Green synthesis of Vitis vinifera extract-appended magnesium oxide NPs for biomedical applications
  52. Differential study on the thermal–physical properties of metal and its oxide nanoparticle-formed nanofluids: Molecular dynamics simulation investigation of argon-based nanofluids
  53. Heat convection and irreversibility of magneto-micropolar hybrid nanofluids within a porous hexagonal-shaped enclosure having heated obstacle
  54. Numerical simulation and optimization of biological nanocomposite system for enhanced oil recovery
  55. Laser ablation and chemical vapor deposition to prepare a nanostructured PPy layer on the Ti surface
  56. Cilostazol niosomes-loaded transdermal gels: An in vitro and in vivo anti-aggregant and skin permeation activity investigations towards preparing an efficient nanoscale formulation
  57. Linear and nonlinear optical studies on successfully mixed vanadium oxide and zinc oxide nanoparticles synthesized by sol–gel technique
  58. Analytical investigation of convective phenomena with nonlinearity characteristics in nanostratified liquid film above an inclined extended sheet
  59. Optimization method for low-velocity impact identification in nanocomposite using genetic algorithm
  60. Analyzing the 3D-MHD flow of a sodium alginate-based nanofluid flow containing alumina nanoparticles over a bi-directional extending sheet using variable porous medium and slip conditions
  61. A comprehensive study of laser irradiated hydrothermally synthesized 2D layered heterostructure V2O5(1−x)MoS2(x) (X = 1–5%) nanocomposites for photocatalytic application
  62. Computational analysis of water-based silver, copper, and alumina hybrid nanoparticles over a stretchable sheet embedded in a porous medium with thermophoretic particle deposition effects
  63. A deep dive into AI integration and advanced nanobiosensor technologies for enhanced bacterial infection monitoring
  64. Effects of normal strain on pyramidal I and II 〈c + a〉 screw dislocation mobility and structure in single-crystal magnesium
  65. Computational study of cross-flow in entropy-optimized nanofluids
  66. Significance of nanoparticle aggregation for thermal transport over magnetized sensor surface
  67. A green and facile synthesis route of nanosize cupric oxide at room temperature
  68. Effect of annealing time on bending performance and microstructure of C19400 alloy strip
  69. Chitosan-based Mupirocin and Alkanna tinctoria extract nanoparticles for the management of burn wound: In vitro and in vivo characterization
  70. Electrospinning of MNZ/PLGA/SF nanofibers for periodontitis
  71. Photocatalytic degradation of methylene blue by Nd-doped titanium dioxide thin films
  72. Shell-core-structured electrospinning film with sequential anti-inflammatory and pro-neurogenic effects for peripheral nerve repairment
  73. Flow and heat transfer insights into a chemically reactive micropolar Williamson ternary hybrid nanofluid with cross-diffusion theory
  74. One-pot fabrication of open-spherical shapes based on the decoration of copper sulfide/poly-O-amino benzenethiol on copper oxide as a promising photocathode for hydrogen generation from the natural source of Red Sea water
  75. A penta-hybrid approach for modeling the nanofluid flow in a spatially dependent magnetic field
  76. Advancing sustainable agriculture: Metal-doped urea–hydroxyapatite hybrid nanofertilizer for agro-industry
  77. Utilizing Ziziphus spina-christi for eco-friendly synthesis of silver nanoparticles: Antimicrobial activity and promising application in wound healing
  78. Plant-mediated synthesis, characterization, and evaluation of a copper oxide/silicon dioxide nanocomposite by an antimicrobial study
  79. Effects of PVA fibers and nano-SiO2 on rheological properties of geopolymer mortar
  80. Investigating silver and alumina nanoparticles’ impact on fluid behavior over porous stretching surface
  81. Potential pharmaceutical applications and molecular docking study for green fabricated ZnO nanoparticles mediated Raphanus sativus: In vitro and in vivo study
  82. Effect of temperature and nanoparticle size on the interfacial layer thickness of TiO2–water nanofluids using molecular dynamics
  83. Characteristics of induced magnetic field on the time-dependent MHD nanofluid flow through parallel plates
  84. Flexural and vibration behaviours of novel covered CFRP composite joints with an MWCNT-modified adhesive
  85. Experimental research on mechanically and thermally activation of nano-kaolin to improve the properties of ultra-high-performance fiber-reinforced concrete
  86. Analysis of variable fluid properties for three-dimensional flow of ternary hybrid nanofluid on a stretching sheet with MHD effects
  87. Biodegradability of corn starch films containing nanocellulose fiber and thymol
  88. Toxicity assessment of copper oxide nanoparticles: In vivo study
  89. Some measures to enhance the energy output performances of triboelectric nanogenerators
  90. Reinforcement of graphene nanoplatelets on water uptake and thermomechanical behaviour of epoxy adhesive subjected to water ageing conditions
  91. Optimization of preparation parameters and testing verification of carbon nanotube suspensions used in concrete
  92. Max-phase Ti3SiC2 and diverse nanoparticle reinforcements for enhancement of the mechanical, dynamic, and microstructural properties of AA5083 aluminum alloy via FSP
  93. Advancing drug delivery: Neural network perspectives on nanoparticle-mediated treatments for cancerous tissues
  94. PEG-PLGA core–shell nanoparticles for the controlled delivery of picoplatin–hydroxypropyl β-cyclodextrin inclusion complex in triple-negative breast cancer: In vitro and in vivo study
  95. Conduction transportation from graphene to an insulative polymer medium: A novel approach for the conductivity of nanocomposites
  96. Review Articles
  97. Developments of terahertz metasurface biosensors: A literature review
  98. Overview of amorphous carbon memristor device, modeling, and applications for neuromorphic computing
  99. Advances in the synthesis of gold nanoclusters (AuNCs) of proteins extracted from nature
  100. A review of ternary polymer nanocomposites containing clay and calcium carbonate and their biomedical applications
  101. Recent advancements in polyoxometalate-functionalized fiber materials: A review
  102. Special contribution of atomic force microscopy in cell death research
  103. A comprehensive review of oral chitosan drug delivery systems: Applications for oral insulin delivery
  104. Cellular senescence and nanoparticle-based therapies: Current developments and perspectives
  105. Cyclodextrins-block copolymer drug delivery systems: From design and development to preclinical studies
  106. Micelle-based nanoparticles with stimuli-responsive properties for drug delivery
  107. Critical assessment of the thermal stability and degradation of chemically functionalized nanocellulose-based polymer nanocomposites
  108. Research progress in preparation technology of micro and nano titanium alloy powder
  109. Nanoformulations for lysozyme-based additives in animal feed: An alternative to fight antibiotic resistance spread
  110. Incorporation of organic photochromic molecules in mesoporous silica materials: Synthesis and applications
  111. A review on modeling of graphene and associated nanostructures reinforced concrete
  112. A review on strengthening mechanisms of carbon quantum dots-reinforced Cu-matrix nanocomposites
  113. Review on nanocellulose composites and CNFs assembled microfiber toward automotive applications
  114. Nanomaterial coating for layered lithium rich transition metal oxide cathode for lithium-ion battery
  115. Application of AgNPs in biomedicine: An overview and current trends
  116. Nanobiotechnology and microbial influence on cold adaptation in plants
  117. Hepatotoxicity of nanomaterials: From mechanism to therapeutic strategy
  118. Applications of micro-nanobubble and its influence on concrete properties: An in-depth review
  119. A comprehensive systematic literature review of ML in nanotechnology for sustainable development
  120. Exploiting the nanotechnological approaches for traditional Chinese medicine in childhood rhinitis: A review of future perspectives
  121. Twisto-photonics in two-dimensional materials: A comprehensive review
  122. Current advances of anticancer drugs based on solubilization technology
  123. Recent process of using nanoparticles in the T cell-based immunometabolic therapy
  124. Future prospects of gold nanoclusters in hydrogen storage systems and sustainable environmental treatment applications
  125. Preparation, types, and applications of one- and two-dimensional nanochannels and their transport properties for water and ions
  126. Microstructural, mechanical, and corrosion characteristics of Mg–Gd–x systems: A review of recent advancements
  127. Functionalized nanostructures and targeted delivery systems with a focus on plant-derived natural agents for COVID-19 therapy: A review and outlook
  128. Mapping evolution and trends of cell membrane-coated nanoparticles: A bibliometric analysis and scoping review
  129. Nanoparticles and their application in the diagnosis of hepatocellular carcinoma
  130. In situ growth of carbon nanotubes on fly ash substrates
  131. Structural performance of boards through nanoparticle reinforcement: An advance review
  132. Reinforcing mechanisms review of the graphene oxide on cement composites
  133. Seed regeneration aided by nanomaterials in a climate change scenario: A comprehensive review
  134. Surface-engineered quantum dot nanocomposites for neurodegenerative disorder remediation and avenue for neuroimaging
  135. Graphitic carbon nitride hybrid thin films for energy conversion: A mini-review on defect activation with different materials
  136. Nanoparticles and the treatment of hepatocellular carcinoma
  137. Special Issue on Advanced Nanomaterials and Composites for Energy Conversion and Storage - Part II
  138. Highly safe lithium vanadium oxide anode for fast-charging dendrite-free lithium-ion batteries
  139. Recent progress in nanomaterials of battery energy storage: A patent landscape analysis, technology updates, and future prospects
  140. Special Issue on Advanced Nanomaterials for Carbon Capture, Environment and Utilization for Energy Sustainability - Part II
  141. Calcium-, magnesium-, and yttrium-doped lithium nickel phosphate nanomaterials as high-performance catalysts for electrochemical water oxidation reaction
  142. Low alkaline vegetation concrete with silica fume and nano-fly ash composites to improve the planting properties and soil ecology
  143. Mesoporous silica-grafted deep eutectic solvent-based mixed matrix membranes for wastewater treatment: Synthesis and emerging pollutant removal performance
  144. Electrochemically prepared ultrathin two-dimensional graphitic nanosheets as cathodes for advanced Zn-based energy storage devices
  145. Enhanced catalytic degradation of amoxicillin by phyto-mediated synthesised ZnO NPs and ZnO-rGO hybrid nanocomposite: Assessment of antioxidant activity, adsorption, and thermodynamic analysis
  146. Incorporating GO in PI matrix to advance nanocomposite coating: An enhancing strategy to prevent corrosion
  147. Synthesis, characterization, thermal stability, and application of microporous hyper cross-linked polyphosphazenes with naphthylamine group for CO2 uptake
  148. Engineering in ceramic albite morphology by the addition of additives: Carbon nanotubes and graphene oxide for energy applications
  149. Nanoscale synergy: Optimizing energy storage with SnO2 quantum dots on ZnO hexagonal prisms for advanced supercapacitors
  150. Aging assessment of silicone rubber materials under corona discharge accompanied by humidity and UV radiation
  151. Tuning structural and electrical properties of Co-precipitated and Cu-incorporated nickel ferrite for energy applications
  152. Sodium alginate-supported AgSr nanoparticles for catalytic degradation of malachite green and methyl orange in aqueous medium
  153. An environmentally greener and reusability approach for bioenergy production using Mallotus philippensis (Kamala) seed oil feedstock via phytonanotechnology
  154. Micro-/nano-alumina trihydrate and -magnesium hydroxide fillers in RTV-SR composites under electrical and environmental stresses
  155. Mechanism exploration of ion-implanted epoxy on surface trap distribution: An approach to augment the vacuum flashover voltages
  156. Nanoscale engineering of semiconductor photocatalysts boosting charge separation for solar-driven H2 production: Recent advances and future perspective
  157. Excellent catalytic performance over reduced graphene-boosted novel nanoparticles for oxidative desulfurization of fuel oil
  158. Special Issue on Advances in Nanotechnology for Agriculture
  159. Deciphering the synergistic potential of mycogenic zinc oxide nanoparticles and bio-slurry formulation on phenology and physiology of Vigna radiata
  160. Nanomaterials: Cross-disciplinary applications in ornamental plants
  161. Special Issue on Catechol Based Nano and Microstructures
  162. Polydopamine films: Versatile but interface-dependent coatings
  163. In vitro anticancer activity of melanin-like nanoparticles for multimodal therapy of glioblastoma
  164. Poly-3,4-dihydroxybenzylidenhydrazine, a different analogue of polydopamine
  165. Chirality and self-assembly of structures derived from optically active 1,2-diaminocyclohexane and catecholamines
  166. Advancing resource sustainability with green photothermal materials: Insights from organic waste-derived and bioderived sources
  167. Bioinspired neuromelanin-like Pt(iv) polymeric nanoparticles for cancer treatment
  168. Special Issue on Implementing Nanotechnology for Smart Healthcare System
  169. Intelligent explainable optical sensing on Internet of nanorobots for disease detection
  170. Special Issue on Green Mono, Bi and Tri Metallic Nanoparticles for Biological and Environmental Applications
  171. Tracking success of interaction of green-synthesized Carbopol nanoemulgel (neomycin-decorated Ag/ZnO nanocomposite) with wound-based MDR bacteria
  172. Green synthesis of copper oxide nanoparticles using genus Inula and evaluation of biological therapeutics and environmental applications
  173. Biogenic fabrication and multifunctional therapeutic applications of silver nanoparticles synthesized from rose petal extract
  174. Metal oxides on the frontlines: Antimicrobial activity in plant-derived biometallic nanoparticles
  175. Controlling pore size during the synthesis of hydroxyapatite nanoparticles using CTAB by the sol–gel hydrothermal method and their biological activities
  176. Special Issue on State-of-Art Advanced Nanotechnology for Healthcare
  177. Applications of nanomedicine-integrated phototherapeutic agents in cancer theranostics: A comprehensive review of the current state of research
  178. Smart bionanomaterials for treatment and diagnosis of inflammatory bowel disease
  179. Beyond conventional therapy: Synthesis of multifunctional nanoparticles for rheumatoid arthritis therapy
https://doi.org/10.1515/ntrev-2023-0212
Keywords for this article
curcumin; zein nanoparticles; bacterial biofilms; antibiotic resistance; healthcare; Pseudomonas aeruginosa
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. Tension buckling and postbuckling of nanocomposite laminated plates with in-plane negative Poisson’s ratio
  3. Polyvinylpyrrolidone-stabilised gold nanoparticle coatings inhibit blood protein adsorption
  4. Energy and mass transmission through hybrid nanofluid flow passing over a spinning sphere with magnetic effect and heat source/sink
  5. Surface treatment with nano-silica and magnesium potassium phosphate cement co-action for enhancing recycled aggregate concrete
  6. Numerical investigation of thermal radiation with entropy generation effects in hybrid nanofluid flow over a shrinking/stretching sheet
  7. Enhancing the performance of thermal energy storage by adding nano-particles with paraffin phase change materials
  8. Using nano-CaCO3 and ceramic tile waste to design low-carbon ultra high performance concrete
  9. Numerical analysis of thermophoretic particle deposition in a magneto-Marangoni convective dusty tangent hyperbolic nanofluid flow – Thermal and magnetic features
  10. Dual numerical solutions of Casson SA–hybrid nanofluid toward a stagnation point flow over stretching/shrinking cylinder
  11. Single flake homo p–n diode of MoTe2 enabled by oxygen plasma doping
  12. Electrostatic self-assembly effect of Fe3O4 nanoparticles on performance of carbon nanotubes in cement-based materials
  13. Multi-scale alignment to buried atom-scale devices using Kelvin probe force microscopy
  14. Antibacterial, mechanical, and dielectric properties of hydroxyapatite cordierite/zirconia porous nanocomposites for use in bone tissue engineering applications
  15. Time-dependent Darcy–Forchheimer flow of Casson hybrid nanofluid comprising the CNTs through a Riga plate with nonlinear thermal radiation and viscous dissipation
  16. Durability prediction of geopolymer mortar reinforced with nanoparticles and PVA fiber using particle swarm optimized BP neural network
  17. Utilization of zein nano-based system for promoting antibiofilm and anti-virulence activities of curcumin against Pseudomonas aeruginosa
  18. Antibacterial effect of novel dental resin composites containing rod-like zinc oxide
  19. An extended model to assess Jeffery–Hamel blood flow through arteries with iron-oxide (Fe2O3) nanoparticles and melting effects: Entropy optimization analysis
  20. Comparative study of copper nanoparticles over radially stretching sheet with water and silicone oil
  21. Cementitious composites modified by nanocarbon fillers with cooperation effect possessing excellent self-sensing properties
  22. Confinement size effect on dielectric properties, antimicrobial activity, and recycling of TiO2 quantum dots via photodegradation processes of Congo red dye and real industrial textile wastewater
  23. Biogenic silver nanoparticles of Moringa oleifera leaf extract: Characterization and photocatalytic application
  24. Novel integrated structure and function of Mg–Gd neutron shielding materials
  25. Impact of multiple slips on thermally radiative peristaltic transport of Sisko nanofluid with double diffusion convection, viscous dissipation, and induced magnetic field
  26. Magnetized water-based hybrid nanofluid flow over an exponentially stretching sheet with thermal convective and mass flux conditions: HAM solution
  27. A numerical investigation of the two-dimensional magnetohydrodynamic water-based hybrid nanofluid flow composed of Fe3O4 and Au nanoparticles over a heated surface
  28. Development and modeling of an ultra-robust TPU-MWCNT foam with high flexibility and compressibility
  29. Effects of nanofillers on the physical, mechanical, and tribological behavior of carbon/kenaf fiber–reinforced phenolic composites
  30. Polymer nanocomposite for protecting photovoltaic cells from solar ultraviolet in space
  31. Study on the mechanical properties and microstructure of recycled concrete reinforced with basalt fibers and nano-silica in early low-temperature environments
  32. Synergistic effect of carbon nanotubes and polyvinyl alcohol on the mechanical performance and microstructure of cement mortar
  33. CFD analysis of paraffin-based hybrid (Co–Au) and trihybrid (Co–Au–ZrO2) nanofluid flow through a porous medium
  34. Forced convective tangent hyperbolic nanofluid flow subject to heat source/sink and Lorentz force over a permeable wedge: Numerical exploration
  35. Physiochemical and electrical activities of nano copper oxides synthesised via hydrothermal method utilising natural reduction agents for solar cell application
  36. A homotopic analysis of the blood-based bioconvection Carreau–Yasuda hybrid nanofluid flow over a stretching sheet with convective conditions
  37. In situ synthesis of reduced graphene oxide/SnIn4S8 nanocomposites with enhanced photocatalytic performance for pollutant degradation
  38. A coarse-grained Poisson–Nernst–Planck model for polyelectrolyte-modified nanofluidic diodes
  39. A numerical investigation of the magnetized water-based hybrid nanofluid flow over an extending sheet with a convective condition: Active and passive controls of nanoparticles
  40. The LyP-1 cyclic peptide modified mesoporous polydopamine nanospheres for targeted delivery of triptolide regulate the macrophage repolarization in atherosclerosis
  41. Synergistic effect of hydroxyapatite-magnetite nanocomposites in magnetic hyperthermia for bone cancer treatment
  42. The significance of quadratic thermal radiative scrutinization of a nanofluid flow across a microchannel with thermophoretic particle deposition effects
  43. Ferromagnetic effect on Casson nanofluid flow and transport phenomena across a bi-directional Riga sensor device: Darcy–Forchheimer model
  44. Performance of carbon nanomaterials incorporated with concrete exposed to high temperature
  45. Multicriteria-based optimization of roller compacted concrete pavement containing crumb rubber and nano-silica
  46. Revisiting hydrotalcite synthesis: Efficient combined mechanochemical/coprecipitation synthesis to design advanced tunable basic catalysts
  47. Exploration of irreversibility process and thermal energy of a tetra hybrid radiative binary nanofluid focusing on solar implementations
  48. Effect of graphene oxide on the properties of ternary limestone clay cement paste
  49. Improved mechanical properties of graphene-modified basalt fibre–epoxy composites
  50. Sodium titanate nanostructured modified by green synthesis of iron oxide for highly efficient photodegradation of dye contaminants
  51. Green synthesis of Vitis vinifera extract-appended magnesium oxide NPs for biomedical applications
  52. Differential study on the thermal–physical properties of metal and its oxide nanoparticle-formed nanofluids: Molecular dynamics simulation investigation of argon-based nanofluids
  53. Heat convection and irreversibility of magneto-micropolar hybrid nanofluids within a porous hexagonal-shaped enclosure having heated obstacle
  54. Numerical simulation and optimization of biological nanocomposite system for enhanced oil recovery
  55. Laser ablation and chemical vapor deposition to prepare a nanostructured PPy layer on the Ti surface
  56. Cilostazol niosomes-loaded transdermal gels: An in vitro and in vivo anti-aggregant and skin permeation activity investigations towards preparing an efficient nanoscale formulation
  57. Linear and nonlinear optical studies on successfully mixed vanadium oxide and zinc oxide nanoparticles synthesized by sol–gel technique
  58. Analytical investigation of convective phenomena with nonlinearity characteristics in nanostratified liquid film above an inclined extended sheet
  59. Optimization method for low-velocity impact identification in nanocomposite using genetic algorithm
  60. Analyzing the 3D-MHD flow of a sodium alginate-based nanofluid flow containing alumina nanoparticles over a bi-directional extending sheet using variable porous medium and slip conditions
  61. A comprehensive study of laser irradiated hydrothermally synthesized 2D layered heterostructure V2O5(1−x)MoS2(x) (X = 1–5%) nanocomposites for photocatalytic application
  62. Computational analysis of water-based silver, copper, and alumina hybrid nanoparticles over a stretchable sheet embedded in a porous medium with thermophoretic particle deposition effects
  63. A deep dive into AI integration and advanced nanobiosensor technologies for enhanced bacterial infection monitoring
  64. Effects of normal strain on pyramidal I and II 〈c + a〉 screw dislocation mobility and structure in single-crystal magnesium
  65. Computational study of cross-flow in entropy-optimized nanofluids
  66. Significance of nanoparticle aggregation for thermal transport over magnetized sensor surface
  67. A green and facile synthesis route of nanosize cupric oxide at room temperature
  68. Effect of annealing time on bending performance and microstructure of C19400 alloy strip
  69. Chitosan-based Mupirocin and Alkanna tinctoria extract nanoparticles for the management of burn wound: In vitro and in vivo characterization
  70. Electrospinning of MNZ/PLGA/SF nanofibers for periodontitis
  71. Photocatalytic degradation of methylene blue by Nd-doped titanium dioxide thin films
  72. Shell-core-structured electrospinning film with sequential anti-inflammatory and pro-neurogenic effects for peripheral nerve repairment
  73. Flow and heat transfer insights into a chemically reactive micropolar Williamson ternary hybrid nanofluid with cross-diffusion theory
  74. One-pot fabrication of open-spherical shapes based on the decoration of copper sulfide/poly-O-amino benzenethiol on copper oxide as a promising photocathode for hydrogen generation from the natural source of Red Sea water
  75. A penta-hybrid approach for modeling the nanofluid flow in a spatially dependent magnetic field
  76. Advancing sustainable agriculture: Metal-doped urea–hydroxyapatite hybrid nanofertilizer for agro-industry
  77. Utilizing Ziziphus spina-christi for eco-friendly synthesis of silver nanoparticles: Antimicrobial activity and promising application in wound healing
  78. Plant-mediated synthesis, characterization, and evaluation of a copper oxide/silicon dioxide nanocomposite by an antimicrobial study
  79. Effects of PVA fibers and nano-SiO2 on rheological properties of geopolymer mortar
  80. Investigating silver and alumina nanoparticles’ impact on fluid behavior over porous stretching surface
  81. Potential pharmaceutical applications and molecular docking study for green fabricated ZnO nanoparticles mediated Raphanus sativus: In vitro and in vivo study
  82. Effect of temperature and nanoparticle size on the interfacial layer thickness of TiO2–water nanofluids using molecular dynamics
  83. Characteristics of induced magnetic field on the time-dependent MHD nanofluid flow through parallel plates
  84. Flexural and vibration behaviours of novel covered CFRP composite joints with an MWCNT-modified adhesive
  85. Experimental research on mechanically and thermally activation of nano-kaolin to improve the properties of ultra-high-performance fiber-reinforced concrete
  86. Analysis of variable fluid properties for three-dimensional flow of ternary hybrid nanofluid on a stretching sheet with MHD effects
  87. Biodegradability of corn starch films containing nanocellulose fiber and thymol
  88. Toxicity assessment of copper oxide nanoparticles: In vivo study
  89. Some measures to enhance the energy output performances of triboelectric nanogenerators
  90. Reinforcement of graphene nanoplatelets on water uptake and thermomechanical behaviour of epoxy adhesive subjected to water ageing conditions
  91. Optimization of preparation parameters and testing verification of carbon nanotube suspensions used in concrete
  92. Max-phase Ti3SiC2 and diverse nanoparticle reinforcements for enhancement of the mechanical, dynamic, and microstructural properties of AA5083 aluminum alloy via FSP
  93. Advancing drug delivery: Neural network perspectives on nanoparticle-mediated treatments for cancerous tissues
  94. PEG-PLGA core–shell nanoparticles for the controlled delivery of picoplatin–hydroxypropyl β-cyclodextrin inclusion complex in triple-negative breast cancer: In vitro and in vivo study
  95. Conduction transportation from graphene to an insulative polymer medium: A novel approach for the conductivity of nanocomposites
  96. Review Articles
  97. Developments of terahertz metasurface biosensors: A literature review
  98. Overview of amorphous carbon memristor device, modeling, and applications for neuromorphic computing
  99. Advances in the synthesis of gold nanoclusters (AuNCs) of proteins extracted from nature
  100. A review of ternary polymer nanocomposites containing clay and calcium carbonate and their biomedical applications
  101. Recent advancements in polyoxometalate-functionalized fiber materials: A review
  102. Special contribution of atomic force microscopy in cell death research
  103. A comprehensive review of oral chitosan drug delivery systems: Applications for oral insulin delivery
  104. Cellular senescence and nanoparticle-based therapies: Current developments and perspectives
  105. Cyclodextrins-block copolymer drug delivery systems: From design and development to preclinical studies
  106. Micelle-based nanoparticles with stimuli-responsive properties for drug delivery
  107. Critical assessment of the thermal stability and degradation of chemically functionalized nanocellulose-based polymer nanocomposites
  108. Research progress in preparation technology of micro and nano titanium alloy powder
  109. Nanoformulations for lysozyme-based additives in animal feed: An alternative to fight antibiotic resistance spread
  110. Incorporation of organic photochromic molecules in mesoporous silica materials: Synthesis and applications
  111. A review on modeling of graphene and associated nanostructures reinforced concrete
  112. A review on strengthening mechanisms of carbon quantum dots-reinforced Cu-matrix nanocomposites
  113. Review on nanocellulose composites and CNFs assembled microfiber toward automotive applications
  114. Nanomaterial coating for layered lithium rich transition metal oxide cathode for lithium-ion battery
  115. Application of AgNPs in biomedicine: An overview and current trends
  116. Nanobiotechnology and microbial influence on cold adaptation in plants
  117. Hepatotoxicity of nanomaterials: From mechanism to therapeutic strategy
  118. Applications of micro-nanobubble and its influence on concrete properties: An in-depth review
  119. A comprehensive systematic literature review of ML in nanotechnology for sustainable development
  120. Exploiting the nanotechnological approaches for traditional Chinese medicine in childhood rhinitis: A review of future perspectives
  121. Twisto-photonics in two-dimensional materials: A comprehensive review
  122. Current advances of anticancer drugs based on solubilization technology
  123. Recent process of using nanoparticles in the T cell-based immunometabolic therapy
  124. Future prospects of gold nanoclusters in hydrogen storage systems and sustainable environmental treatment applications
  125. Preparation, types, and applications of one- and two-dimensional nanochannels and their transport properties for water and ions
  126. Microstructural, mechanical, and corrosion characteristics of Mg–Gd–x systems: A review of recent advancements
  127. Functionalized nanostructures and targeted delivery systems with a focus on plant-derived natural agents for COVID-19 therapy: A review and outlook
  128. Mapping evolution and trends of cell membrane-coated nanoparticles: A bibliometric analysis and scoping review
  129. Nanoparticles and their application in the diagnosis of hepatocellular carcinoma
  130. In situ growth of carbon nanotubes on fly ash substrates
  131. Structural performance of boards through nanoparticle reinforcement: An advance review
  132. Reinforcing mechanisms review of the graphene oxide on cement composites
  133. Seed regeneration aided by nanomaterials in a climate change scenario: A comprehensive review
  134. Surface-engineered quantum dot nanocomposites for neurodegenerative disorder remediation and avenue for neuroimaging
  135. Graphitic carbon nitride hybrid thin films for energy conversion: A mini-review on defect activation with different materials
  136. Nanoparticles and the treatment of hepatocellular carcinoma
  137. Special Issue on Advanced Nanomaterials and Composites for Energy Conversion and Storage - Part II
  138. Highly safe lithium vanadium oxide anode for fast-charging dendrite-free lithium-ion batteries
  139. Recent progress in nanomaterials of battery energy storage: A patent landscape analysis, technology updates, and future prospects
  140. Special Issue on Advanced Nanomaterials for Carbon Capture, Environment and Utilization for Energy Sustainability - Part II
  141. Calcium-, magnesium-, and yttrium-doped lithium nickel phosphate nanomaterials as high-performance catalysts for electrochemical water oxidation reaction
  142. Low alkaline vegetation concrete with silica fume and nano-fly ash composites to improve the planting properties and soil ecology
  143. Mesoporous silica-grafted deep eutectic solvent-based mixed matrix membranes for wastewater treatment: Synthesis and emerging pollutant removal performance
  144. Electrochemically prepared ultrathin two-dimensional graphitic nanosheets as cathodes for advanced Zn-based energy storage devices
  145. Enhanced catalytic degradation of amoxicillin by phyto-mediated synthesised ZnO NPs and ZnO-rGO hybrid nanocomposite: Assessment of antioxidant activity, adsorption, and thermodynamic analysis
  146. Incorporating GO in PI matrix to advance nanocomposite coating: An enhancing strategy to prevent corrosion
  147. Synthesis, characterization, thermal stability, and application of microporous hyper cross-linked polyphosphazenes with naphthylamine group for CO2 uptake
  148. Engineering in ceramic albite morphology by the addition of additives: Carbon nanotubes and graphene oxide for energy applications
  149. Nanoscale synergy: Optimizing energy storage with SnO2 quantum dots on ZnO hexagonal prisms for advanced supercapacitors
  150. Aging assessment of silicone rubber materials under corona discharge accompanied by humidity and UV radiation
  151. Tuning structural and electrical properties of Co-precipitated and Cu-incorporated nickel ferrite for energy applications
  152. Sodium alginate-supported AgSr nanoparticles for catalytic degradation of malachite green and methyl orange in aqueous medium
  153. An environmentally greener and reusability approach for bioenergy production using Mallotus philippensis (Kamala) seed oil feedstock via phytonanotechnology
  154. Micro-/nano-alumina trihydrate and -magnesium hydroxide fillers in RTV-SR composites under electrical and environmental stresses
  155. Mechanism exploration of ion-implanted epoxy on surface trap distribution: An approach to augment the vacuum flashover voltages
  156. Nanoscale engineering of semiconductor photocatalysts boosting charge separation for solar-driven H2 production: Recent advances and future perspective
  157. Excellent catalytic performance over reduced graphene-boosted novel nanoparticles for oxidative desulfurization of fuel oil
  158. Special Issue on Advances in Nanotechnology for Agriculture
  159. Deciphering the synergistic potential of mycogenic zinc oxide nanoparticles and bio-slurry formulation on phenology and physiology of Vigna radiata
  160. Nanomaterials: Cross-disciplinary applications in ornamental plants
  161. Special Issue on Catechol Based Nano and Microstructures
  162. Polydopamine films: Versatile but interface-dependent coatings
  163. In vitro anticancer activity of melanin-like nanoparticles for multimodal therapy of glioblastoma
  164. Poly-3,4-dihydroxybenzylidenhydrazine, a different analogue of polydopamine
  165. Chirality and self-assembly of structures derived from optically active 1,2-diaminocyclohexane and catecholamines
  166. Advancing resource sustainability with green photothermal materials: Insights from organic waste-derived and bioderived sources
  167. Bioinspired neuromelanin-like Pt(iv) polymeric nanoparticles for cancer treatment
  168. Special Issue on Implementing Nanotechnology for Smart Healthcare System
  169. Intelligent explainable optical sensing on Internet of nanorobots for disease detection
  170. Special Issue on Green Mono, Bi and Tri Metallic Nanoparticles for Biological and Environmental Applications
  171. Tracking success of interaction of green-synthesized Carbopol nanoemulgel (neomycin-decorated Ag/ZnO nanocomposite) with wound-based MDR bacteria
  172. Green synthesis of copper oxide nanoparticles using genus Inula and evaluation of biological therapeutics and environmental applications
  173. Biogenic fabrication and multifunctional therapeutic applications of silver nanoparticles synthesized from rose petal extract
  174. Metal oxides on the frontlines: Antimicrobial activity in plant-derived biometallic nanoparticles
  175. Controlling pore size during the synthesis of hydroxyapatite nanoparticles using CTAB by the sol–gel hydrothermal method and their biological activities
  176. Special Issue on State-of-Art Advanced Nanotechnology for Healthcare
  177. Applications of nanomedicine-integrated phototherapeutic agents in cancer theranostics: A comprehensive review of the current state of research
  178. Smart bionanomaterials for treatment and diagnosis of inflammatory bowel disease
  179. Beyond conventional therapy: Synthesis of multifunctional nanoparticles for rheumatoid arthritis therapy
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 5.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/ntrev-2023-0212/html
Scroll to top button