Graphical abstract

Abstract
Herein, we report on the development of chitosan-capped silver nanoparticles (AgNPs-CHI) with an intrinsic activity against breast cancer cells. Following chemical synthesis via a simple, one-pot reaction, the chitosan coating of AgNPs was verified using Fourier-transform infrared and ultraviolet–visible spectroscopies. The physicochemical properties and morphology were characterized using dynamic light scattering, scanning electron microscopy, and transmission electron microscopy. The shelf stability of the optimized platform was tracked for 3 months upon storage at either room temperature or 4°C. Then, the anticancer activities of AgNPs-CHI on human breast cancer cells, MCF-7, versus normal human cells, human skin fibroblasts (HSF), were evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity assay and tumor-associated biomarkers determination by enzyme-linked immunosorbent assay, in comparison with plain silver nitrate (AgNO3) solution. AgNPs were successfully coated with chitosan and demonstrated acceptable physicochemical properties, with a spherical morphology and high stability upon long-term storage. Although AgNPs-CHI and AgNO3 demonstrated comparable cytotoxicity to MCF-7 cells, AgNPs-CHI resulted in 10-fold lower toxicity to HSF cells, suggesting a higher selectivity. In addition, AgNPs-CHI lowered IL-6 and tumor necrosis factor-alpha levels in MCF-7 cells by 90 and 30%, respectively, compared to 60 and 10% in the case of plain AgNO3. The interesting therapeutic modality presented in this study is promising for potential clinical applications.
1 Introduction
Cancer is a leading cause of death across the globe [1,2]. Breast cancer is still the most common and widely spread cancer in females. It has been recently estimated in 2020 that approximately 2.261 million new cases and 0.685 million deaths are related to this type of cancer globally [3]. It is also a multifunctional disorder with a high degree of inter-tumoral and intra-tumoral molecular and morphological heterogeneity [4]. The treatment strategy and clinical decision depend on the tumor subtype according to the estimated biomarkers and the pathophysiological and clinically collected data [5,6]. Non-selective or non-targeted therapy based on conventional chemotherapeutics is a two-edged weapon, considering its detrimental effects on healthy tissues. In addition, the tricky physicochemical properties of these agents, such as low aqueous solubility, poor diffusion into the tumor mass, and systemic toxicity, have collectively obliged scientists to develop new formulations to tackle these problems [7,8,9]. Different nanomaterials and their drug conjugates have shown promise and successful applications, especially in breast adenocarcinoma management [10,11]. Moreover, nanomedicines can act as a platform for the bioimaging of tumors [12].
Inorganic/metallic nanoparticles have attracted attention recently owing to their ease of fabrication, scalability, and interesting properties [13,14]. Silver nanoparticles (AgNPs) are considered the most relevant type of metallic nanomaterials in the area of anticancer therapeutics owing to their genotoxic effects and capability of programmed apoptosis induction [15,16]. In addition, it has been revealed that AgNPs can also modulate some interactions with the stromal cells and immune cells in the tumor microenvironment, which subsequently promote anticancer activity [17]. Increasing number of recent studies have demonstrated the high potential of AgNPs in the treatment of a wide variety of cancers including lung cancer, melanoma, hepatocellular carcinoma, glioma, prostate cancer, and multidrug-resistant tumors [18,19,20]. Moreover, it has also been demonstrated by other researchers that AgNPs have a potential role in the treatment of breast cancer [21,22,23]. Capping AgNPs with different polymeric materials can modulate their physicochemical properties, biodistribution, nanoparticles–cells interactions, cellular uptake, and intracellular silver ion release, which subsequently affect the selectivity, cytotoxic efficiency, and biosafety [24,25]. Pinzaru and coworkers reported on the increased stability and biotolerability of polyethylene glycol (PEG)-coated AgNPs [26]. A recent study performed in our group has shown the significant effect of AgNPs coated with ethyl cellulose on the inhibition of Tumor Necrosis Factor-alpha (TNF-α) in the breast cancer cell line, MCF-7 [27].
Chitosan (CHI) is a carbohydrate-based biopolymer that has been extensively investigated in the pharmaceutical literature as either a drug carrier or a coating material thanks to its ease of synthesis, economic price, biodegradability, and compatibility with most materials of pharmaceutical interest [28]. CHI has been investigated as a stabilizer and a functional coating for several metallic nanoparticles including platinum nanoparticles, gold nanoparticles, and copper nanoparticles [29,30].
In the present study, we investigated the impact of coating AgNPs with CHI on their performance against breast cancer cells. Our results revealed that chitosan-capped AgNPs (AgNPs-CHI) demonstrated an interesting potent and selective intrinsic anticancer activity against human breast adenocarcinoma cells, MCF-7, compared to a normal human cell model, human skin fibroblasts (HSF) cell line, as evidenced by a significant reduction in cell viability, Interleukin-6 (IL-6), and TNF-α levels. In contrast, plain silver nitrate solution (AgNO3) showed significantly lower effects on the investigated tumor-associated biomarkers as well as non-selective cytotoxic effects, with severe damage to normal human cells. The therapeutic modality presented in this study holds promise as a non-classical treatment for breast cancer.
2 Materials and methods
2.1 Materials
Low molecular weight chitosan (50–190 kDa) and medium molecular weight chitosan (190–310 kDa) were purchased from Sigma Aldrich, USA. Human breast cancer cells (MCF-7) and HSF were obtained from American Type Culture Collection, USA, and were cultured and maintained according to the manufacturer’s recommendations. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay kit was purchased from Abcam, UK. Quantikine® ELISA kits for human IL-6 and TNF-α were obtained from R&D Systems, USA. Bicinchoninic acid protein assay kit, radioimmunoprecipitation assay (RIPA) buffer, protease inhibitors, and phosphatase inhibitors were obtained from Thermofisher Scientific, USA. All the other used chemical reagents were of analytical grades and were used without further processing.
2.2 Preparation of AgNPs-CHI
Chitosan-coated AgNPs (AgNPs-CHI) were prepared according to the method reported by Mi et al. [31]. Fifty milligrams of CHI was dissolved in 10 mL of an aqueous solution of glacial acetic acid (10.0% v/v). Then, 5 mL of 1 mM AgNO3 aqueous solution was added to the CHI solution, which was then diluted to 100 mL with distilled water. The solution was maintained in an ice bath with a constant stirring for 10 min. Reduction of AgNO3 was mediated via the addition of 60 µL of 0.1 M sodium borohydride (NaBH4) dropwise while stirring for 45–60 min. Finally, the obtained AgNPs-CHI solution was kept at room temperature for another 15–30 min while being stirred. AgNPs-CHI dispersion was centrifuged, and then, the obtained pellets were dispersed in distilled water for being investigated in the subsequent experiments.
2.3 Characterization of AgNPs-CHI
2.3.1 Dynamic light scattering (DLS) studies
The geometrical particle size and the charge (ζ potential) of the produced AgNPs-CHI were determined by DLS using the Zetasizer Nano ZS analyzer (Malvern Instruments, UK) [32]. Simply, samples were adjusted to ∼25°C and then exposed to a laser beam of ≈633 nm at a scattering angle of ≈90°. Samples were run 20 times, with a run time of 10 s. The average measurement of 3–6 formulations was considered and presented ± standard deviation.
2.3.2 Ultraviolet-visible (UV-Vis) spectroscopy
AgNPs-CHI solution was scanned from 300 to 600 nm using UV-VIS Spectrophotometer (Lambda 25, Perkin Elmer, Singapore). The absorbance spectra were plotted against the investigated wavelengths [33].
2.3.3 Fourier-transform infrared spectroscopy (FT-IR)
FT-IR spectrometer (Alpha II, model: Bruker, USA) was used to investigate the possible interaction and or coating of AgNPs with CHI. Spectra were collected from Solutions of medium molecular weight CHI, AgNO3 (as a reference for silver), and AgNPs-CHI after their scanning from 4,000 to 400 cm−1 as described previously [34].
2.3.4 Scanning electron microscopy (SEM)
The morphology and aggregation status of the optimized AgNPs-CHI were examined using an SEM microscope (Zeiss EVO LS10, Cambridge, UK), as described previously [35]. Samples were fitted to the stubs using a double-sided adhesive carbon tape and coated with gold under a vacuum in an atmosphere of the Argon gas for 120 s, prior to scanning and imaging using either a low magnification power or a high magnification power.
2.3.5 Transmission electron microscopy (TEM)
TEM was used to observe the morphology of the optimized AgNPs-CHI and estimate their particle diameter. Briefly, 10 µL of AgNPs-CHI solution was dropped onto the double-sided copper conductive tape surface and was allowed to dry overnight. Nanoparticles were visualized under the TEM microscope at 10–100k magnification power using an accelerating voltage of 100 kV. (JEM-1230, JEOL, Japan) [36].
2.4 Physical stability assessment
The stability of the optimized AgNPs-CHI against aggregation was investigated after storage for 3 months at two different conditions: room temperature (∼25°C) and 4.0 ± 0.5°C. The physical appearance of nanoparticles, including their color and morphology in addition to their particle size and zeta potential, were investigated at the beginning and the end of the storage period to judge their shelf stability.
2.5 Cytotoxicity study
The in vitro cytotoxicity of CHI, AgNPs-CHI, and AgNO3 solutions was evaluated on MCF-7 cells versus HSF cells using MTT assay as reported previously [37]. Briefly, 3
2.6 Evaluation of tumor-associated biomarkers
The tumor-associated biomarkers, IL-6 and TNF-α, were assessed using an enzyme-linked immunosorbent assay (ELISA) as reported previously [32,38]. Sandwich ELISA protocol was adopted using pre-coated Quantikine® kits according to the manufacturer’s recommendations. Cells were seeded as described earlier and treated with the investigated samples at concentrations corresponding to their IC50 values for 48 h. Then, the cells were lysed using RIPA buffer supplemented with protease/phosphatase inhibitors, and the cell lysate was centrifuged at 15,000g, 4°C for 10 min followed by protein quantification via BCA assay. Samples were diluted with deionized water to obtain a working protein concentration of 1 mg/mL. Fifty microliters of the tested samples was then diluted with an equal volume of the specific assay diluent solution prior to their introduction into the pre-coated ELISA plates and incubated at room temperature for 2 h. The plates were washed with wash buffer, treated with biotinylated antibodies, and incubated at room temperature for extra 2 h followed by washing. A polymeric solution of horse radish peroxidase (HRP)–streptavidin was added to conjugate to the biotinylated antibodies and the color reaction is formed by the addition of tetramethylbenzidine (TMB) substrate solution. The color reaction was stopped with the kit’s stop solution, and the absorbance was measured at 450 nm with correction by subtracting the readings at 540 or 570 nm. The biomarker concentration was calculated from a pre-constructed calibration curve and compared to the values of non-treated cells that were processed similarly.
2.7 Statistical analysis
Statistical analysis was performed using Graphpad Prism 8 software. One-way analysis of variance (ANOVA) followed by the Bonferroni test was used for multiple comparisons in a single cell line (one-factor experiments), while two-way ANOVA followed by the Bonferroni test was used for multiple comparisons in different cell lines (two-factor experiments). P ≤ 0.05 was considered to be statistically significant.
3 Results
3.1 Preparation and characterization of AgNPs-CHI
The efficiency of AgNPs-CHI synthesis was confirmed by the color change of the reaction medium to the characteristic yellow color 15 min following the addition of NaBH4 solution.
To select the top-performing functional coating for AgNPs, CHI polymers with two different molecular weight ranges were investigated; namely low molecular weight CHI (50–190 kDa) and medium molecular weight CHI (190–310 kDa). The physicochemical properties of the resultant AgNPs were evaluated using DLS (Table 1 and Figure 1). The results revealed better physicochemical performance for the medium molecular weight CHI-coated AgNPs. Consequently, they were used for further experiments and referred to as chitosan-capped AgNPs (AgNPs-CHI) in the subsequent sections of this article (more details on the DLS images are shown Figures S1–S4).
Comparison of the physicochemical properties of AgNPs coated with chitosan polymers with two different molecular weight ranges (n = 6, average ± standard deviation)*
Hydrodynamic diameter (nm) | PDI | ζ Potential (mV) | |
---|---|---|---|
Low molecular weight | 623.66 ± 55.5 | 0.583 ± 0.09 | 8.67 ± 2.74 |
Medium molecular weight | 287.43 ± 1.89 | 0.411 ± 0.06 | 50.63 ± 2.2 |
- *
The physicochemical properties were evaluated using DLS.

DLS of mean size (nm), zeta potential (mV), and polydispersity index of the formulated silver nanoparticles reduced with low and med molecular weight chitosan.
The efficiency of the functional coating was characterized by UV-VIS and FT-IR spectroscopies. AgNPs-CHI demonstrated a single-band UV absorption spectrum with a maximum absorption wavelength (λ max) of 405 nm (Figure 2). FT-IR spectra of plain AgNO3, used as a reference, are shown in Figure 3a. Pure CHI demonstrated a broadband, with a peak at 3451.57 cm−1, which refers to N–H and O–H stretching, and a characteristic double-spike peak at 1712.79 cm−1 and 1636.89 cm−1 for the NH2 group (Figure 3b). AgNPs-CHI retained the reference peaks of silver, while the double-spike peak of CHI disappeared (Figure 3c).

UV-Vis spectrum of the optimized AgNPs-CHI.

(a) FT-IR spectra of plain AgNO3, (b) medium molecular weight chitosan (CHI), and (c) AgNPs-CHI.
The morphology of the optimized AgNPs-CHI was examined by SEM, where the micrographs revealed spherical nanoparticles, with uniform particle size and a minimal degree of aggregation (Figure 4). Moreover, TEM micrographs of AgNPs-CHI showed spherical non-aggregated particles with a metallic core having an average size of 20.88 ± 2.57 nm (Figure 5).

Examination of the morphology of the optimized AgNPs-CHI by SEM at (a) low magnification and (b) high magnification. Scale bars represent 1 and 0.5 µm, respectively.

Examination of the morphology of the optimized AgNPs-CHI by TEM. The scale bar represents 100 nm.
3.2 Physical stability assessment
AgNPs-CHI demonstrated high stability at the two investigated storage temperature conditions. They did not show any color change or precipitation during the 3-month evaluation period. Moreover, the physicochemical properties of AgNPs-CHI showed negligible changes after storage at either room temperature or 4°C, in comparison with the freshly-prepared counterparts (Table 2).
The physicochemical properties of AgNPs-CHI after a 3-month storage period at different conditions (n = 6, average ± standard deviation)*
Hydrodynamic diameter (nm) | PDI | ζ Potential (mV) | |
---|---|---|---|
Freshly prepared | 287.43 ± 1.89 | 0.411 ± 0.06 | 50.63 ± 2.2 |
Stored at 4°C | 293.68 ± 2.88 | 0.405 ± 0.09 | 52.21 ± 3.1 |
Stored at room temperature | 290.53 ± 3.54 | 0.428 ± 0.11 | 49.32 ± 1.7 |
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*The physicochemical properties were evaluated using DLS.
3.3 Evaluation of the anticancer activities of AgNPs-CHI
The anticancer performance of AgNPs-CHI was evaluated in MCF-7 cells (cancerous model) versus HSF cells (normal model) using cytotoxicity and ELISA assays. Interestingly, both AgNPs-CHI and plain AgNO3 solutions demonstrated an intrinsic anticancer activity on MCF-7 cells with comparable cytotoxic effects, where the IC50 values were 8.6 ± 1.6 and 10.86 ± 2.53 µg/mL for AgNPs-CHI and AgNO3, respectively. Meanwhile, the CHI itself had a far lower toxicity with IC50 ∼ 100 µg/mL. Surprisingly, AgNPs-CHI showed approximately 10-fold lower toxicity to HSF cells compared to AgNO3 (IC50 values were 29.63 ± 4.32 and 3.35 ± 0.5 µg/mL, respectively) (Figure 6a). Furthermore, AgNPs-CHI resulted in ∼90% inhibition of IL-6 and ∼30% inhibition of TNF-α in MCF-7 cells compared to only ∼60% and ∼10% inhibition of the same tumor markers in the case of AgNO3 (Figure 6b and c).

AgNPs-CHI exerts a potent and selective intrinsic anticancer activity against MCF-7 cells. (a) Half-maximal inhibitory concentration (IC50) values of AgNPs-CHI and AgNO3 solutions evaluated on breast cancer cells (MCF-7) and normal human cells (HSF) 48 h post treatment. *P < 0.05, #P < 0.0001. (b) Relative levels of Interleukin 6 (IL-6) in MCF-7 cells lysates 48 h post treatment with AgNPs-CHI or AgNO3 solutions at their corresponding IC50 values. **P < 0.01, #P < 0.0001 versus non-treated cells. ***P < 0.001 for AgNPs-CHI versus AgNO3. (c) Relative levels of TNF-α in MCF-7 cells lysates 48 h post treatment with AgNPs-CHI or AgNO3 solutions at their corresponding IC50 values. *P < 0.05, ***P < 0.001 versus non-treated cells. **P < 0.01 for AgNPs-CHI versus AgNO3. In all panels, n = 3, results are expressed as mean ± standard deviation.
4 Discussion
AgNPs are inorganic nanomedicines with a high potential for various therapeutic applications. Most previous studies investigated the application of AgNPs as drug carriers [39]. Nevertheless, the investigation of the intrinsic drug activities of AgNPs is still premature. Some previous reports discussed the potential cytotoxic activities of AgNPs which may be mediated via the induction of genotoxicity through interaction with the cellular DNA, and the subsequent induction of apoptosis [40]. Buttacavoli and co-workers reported on the maximum accumulation of Ag+ in the mitochondria and nuclei following the cellular uptake of AgNPs [41]. Yet, extending such property to the clinical level is still risky, taking into consideration the off-target toxicity that might be caused by the non-selective AgNPs. Our group has been investigating the functional coating of AgNPs aiming at modulating their efficiency and selectivity [27]. In the present study, we investigated the impact of coating with CHI on the intrinsic anticancer activity of AgNPs, applying breast cancer as a tumor model.
We investigated CHI with two different molecular weight ranges. Coating AgNPs with low molecular weight CHI resulted in nanoparticles with a larger particle size, a higher polydispersity, and a lower zeta potential, in comparison with those coated with medium molecular weight CHI. This may be attributed to the lower spreadability of the low molecular weight CHI, resulting in an inefficient coating [42,43]. In addition, the low zeta potential resulting from such an inefficient coating might have allowed a higher aggregation tendency of AgNPs due to the low repulsive forces, with a subsequent increase in the particle size and particle size polydispersity [44]. Previous reports demonstrated that aggregation of AgNPs has a negative impact on their cytotoxic activity [45,46]. On the other hand, other reports pointed out that the ultra-fine nature of some AgNPs formulations may also exert a negative impact on their colloidal stability and biological performance [47,48]. Considering the earlier considerations, AgNPs with a moderate particle size and a high zeta potential would be favorable from a biological point of view. Therefore, medium molecular weight CHI was selected for further investigations. The optimized AgNPs-CHI demonstrated acceptable size and polydispersity, while the highly-positive zeta potential suggested successful coating of AgNPs with CHI. In addition, UV-Vis spectroscopy confirmed the successful formation of AgNPs, as evidenced by the strong absorption band in the visible region owing to their pronounced surface plasmon resonance effect. AgNPs-CHI spectrum had a maximum absorption wavelength (λ max) of 405 nm, which revealed a successful preparation of AgNPs as well as a spherical morphology of the obtained particles [49]. Furthermore, symmetrical particle size distribution was also predicted from the presence of one absorption band as reported previously [50]. FT-IR spectra confirmed the successful coating of AgNPs with CHI, as suggested by the disappearance of the double-spike peak of the NH2 group of the pure CHI, which indicated a strong interaction between the NH2 group in CHI and the silver [51]. Examination of the optimized AgNPs-CHI by various electron microscopes, SEM and TEM, confirmed their spherical morphology and colloidal stability. Meanwhile, the size values shown by TEM were mostly corresponding to the metallic silver core, contrary to the DLS measurements that showed the hydrodynamic diameter of the whole nanoparticle [52].
Interestingly, the AgNPs-CHI demonstrated high physical stability upon long-term storage at either room temperature or 4°C. This high stability may be attributed to the high zeta potential imparted by the CHI coating, which minimized interactions between the nanoparticles and inhibited the formation of aggregates [53]. Furthermore, the capability of AgNPs-CHI to retain their stability and physicochemical properties after prolonged storage at room temperature is an amazing advantage that promotes their clinical potential, unlike the vast majority of nanomedicines [13].
The functional coating of AgNPs retained their cytotoxicity to MCF-7 cells, as evidenced by a comparable IC50 value to that of the plain AgNO3. Pure CHI showed minimal cytotoxicity to MCF-7 cells, which excludes its additive cytotoxic effect on the overall cell viability evaluated by the MTT assay in the case of AgNPs-CHI and suggests high tolerability. Surprisingly, the functional coating with CHI resulted in a dramatic improvement in the selectivity of MCF-7 cells in comparison with a normal human cell line, HSF. Although we are still investigating the exact mechanism accounting for such a phenomenon, there are possible reasons that can be considered. First, the increased metabolic activity by cancer cells increases their affinity to carbohydrates and their associated polymers such as CHI, with a subsequent higher cellular uptake of CHI-coated particles by cancer cells compared to normal cells [41]. Second, it has been reported that the polyanionic Heparan Sulfate Proteoglycans (HSPGs) are upregulated in the cellular membranes of cancer cells, which increases their affinity to positively charged particles like AgNPs-CHI (zeta potential ∼50 mV) [54,55,56]. Third, CHI has an acidic acid dissociation constant (pK a) ∼6.5 which may favor its protonation in the acidic tumorous microenvironment of MCF-7 cells compared to the normal cells, with a subsequent improvement in the cellular uptake [57,58]. Fourth, CHI may modulate the intracellular release of Ag+ and the interactions with the subcellular organelles such as mitochondria and nucleus following the cellular uptake, which can be speculated from the improved inhibitory effects on IL-6 and TNF-α in comparison with the plain uncoated AgNO3 [59,60]. On the other hand, the plain AgNO3 resulted in non-selective cytotoxicity which was mostly irrelevant to the anticancer activity, as indicated by their inferior impact on IL-6 and TNF-α. Figure 7 outlines the proposed mechanism of the selective cytotoxic effect of AgNPs-CHI against breast cancer cells.

An illustration outlining the proposed mechanism of the selective anticancer activity of AgNPs-CHI against breast cancer cells. The acidic tumor microenvironment promotes the protonation of chitosan, which may improve the interactions of AgNPs-CHI with the polyanionic HSPGs that are overexpressed on the cancer cells. Following the cellular uptake, the chitosan functional coating modulates the intracellular release of silver ions that accumulate into the nucleus resulting in genotoxicity, and in the mitochondria with subsequent disruption of the energy production, which collectively induces cellular apoptosis. Abbreviations: AgNPs-CHI, chitosan-capped silver nanoparticles; HSPGs, heparan sulfate proteoglycans. The figure was created with BioRender.com software, with a publication license (YS24N8UP2Z).
Although some previous studies pointed to the cytotoxic effects of AgNPs against MCF-7 cells, the results shown in the present study were significantly better. A previous analysis by Tao et al. revealed that uncoated AgNPs induced cytotoxicity to MCF-7 cells at IC50 of 150 µg/mL [61]. Similarly, in a second study by Sangour et al., the IC50 of the uncoated AgNPs on the same cell line was higher than 100 µg/mL [62]. In a third study by Hepokur and co-workers, uncoated AgNPs did not show a significant cytotoxicity to MCF-7 cells until being loaded with the cytotoxic drug, capecitabine, which then demonstrated an IC50 of 41.25 μg/mL [63]. Upon comparing these findings with our present results, the value of CHI coating, investigated in the present study, can be speculated. We believe that the amazing finding presented in this study would be promising for future clinical applications, considering the collective advantages of the prepared AgNPs-CHI including the one-pot scalable preparation method, high stability at room temperature, high potency, high selectivity, and high biotolerability. Furthermore, the intrinsic drug-free anticancer activity of AgNPs-CHI is promising to reduce their production cost and extend their industrial applicability as a novel anticancer therapeutic modality.
5 Conclusions
We investigated the impact of the functional coating of AgNPs with CHI on their physicochemical and biological performance on breast cancer cells. Coating AgNPs with medium molecular weight CHI resulted in better physicochemical properties compared to the low molecular weight polymer. Spectroscopical analyses confirmed the successful functional coating of AgNPs. AgNPs-CHI demonstrated a high physical stability for up to 3 months upon storage either at room temperature or at 4°C. AgNPs-CHI demonstrated a potent and selective anticancer activity on breast cancer cells compared to normal human cells, with a significant inhibitory effect on IL-6 and TNF-α, contrary to the plain AgNO3 which resulted in non-selective cytotoxicity and inferior effects on the relevant tumor markers. The novel, scalable, stable, economic, selective, and drug-free therapeutic modality presented in this study is highly promising for potential clinical applications in the treatment of breast cancer, which would overcome the shortcomings of the existing chemotherapeutics. We are proceeding with its in vivo applicability in our upcoming research.
Acknowledgments
The researchers would like to thank the Deanship of Scientific Research, Qassim University, for funding this project. The authors also thank Qassim University for providing technical support.
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Funding information: The authors extend their appreciation to the Deputyship for Research and Innovation, Ministry of Education, Saudi Arabia, for funding this research work through project number (QU-IF-1-2-1). The authors also thank the technical support of Qassim University.
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Author contributions: Ahmed A. H. Abdellatif: conceptualization, investigation, methodology, data curation, validation, writing-review and editing, and funding acquisition; Ahmed Abdelfattah: methodology, investigation, and data curation. Mahmoud A. Younis: data curation, validation, visualization, and writing the manuscript draft. Saed M. Aldalaan: visualization, methodology, data curation, and validation. Hesham M. Tawfeek: conceptualization, investigation, methodology, supervision, and writing-review and editing. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Conflict of interest: The authors state no conflict of interest.
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Data availability statement: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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This work is licensed under the Creative Commons Attribution 4.0 International License.
Articles in the same Issue
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- Preparation of CdS–Ag2S nanocomposites by ultrasound-assisted UV photolysis treatment and its visible light photocatalysis activity
- Significance of nanoparticle radius and inter-particle spacing toward the radiative water-based alumina nanofluid flow over a rotating disk
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- Dynamic recrystallization behavior and nucleation mechanism of dual-scale SiCp/A356 composites processed by P/M method
- High mechanical performance of 3-aminopropyl triethoxy silane/epoxy cured in a sandwich construction of 3D carbon felts foam and woven basalt fibers
- Applying solution of spray polyurea elastomer in asphalt binder: Feasibility analysis and DSR study based on the MSCR and LAS tests
- Study on the chronic toxicity and carcinogenicity of iron-based bioabsorbable stents
- Influence of microalloying with B on the microstructure and properties of brazed joints with Ag–Cu–Zn–Sn filler metal
- Thermohydraulic performance of thermal system integrated with twisted turbulator inserts using ternary hybrid nanofluids
- Study of mechanical properties of epoxy/graphene and epoxy/halloysite nanocomposites
- Effects of CaO addition on the CuW composite containing micro- and nano-sized tungsten particles synthesized via aluminothermic coupling with silicothermic reduction
- Cu and Al2O3-based hybrid nanofluid flow through a porous cavity
- Design of functional vancomycin-embedded bio-derived extracellular matrix hydrogels for repairing infectious bone defects
- Study on nanocrystalline coating prepared by electro-spraying 316L metal wire and its corrosion performance
- Axial compression performance of CFST columns reinforced by ultra-high-performance nano-concrete under long-term loading
- Tungsten trioxide nanocomposite for conventional soliton and noise-like pulse generation in anomalous dispersion laser cavity
- Microstructure and electrical contact behavior of the nano-yttria-modified Cu-Al2O3/30Mo/3SiC composite
- Melting rheology in thermally stratified graphene-mineral oil reservoir (third-grade nanofluid) with slip condition
- Re-examination of nonlinear vibration and nonlinear bending of porous sandwich cylindrical panels reinforced by graphene platelets
- Parametric simulation of hybrid nanofluid flow consisting of cobalt ferrite nanoparticles with second-order slip and variable viscosity over an extending surface
- Chitosan-capped silver nanoparticles with potent and selective intrinsic activity against the breast cancer cells
- Multi-core/shell SiO2@Al2O3 nanostructures deposited on Ti3AlC2 to enhance high-temperature stability and microwave absorption properties
- Solution-processed Bi2S3/BiVO4/TiO2 ternary heterojunction photoanode with enhanced photoelectrochemical performance
- Electroporation effect of ZnO nanoarrays under low voltage for water disinfection
- NIR-II window absorbing graphene oxide-coated gold nanorods and graphene quantum dot-coupled gold nanorods for photothermal cancer therapy
- Nonlinear three-dimensional stability characteristics of geometrically imperfect nanoshells under axial compression and surface residual stress
- Investigation of different nanoparticles properties on the thermal conductivity and viscosity of nanofluids by molecular dynamics simulation
- Optimized Cu2O-{100} facet for generation of different reactive oxidative species via peroxymonosulfate activation at specific pH values to efficient acetaminophen removal
- Brownian and thermal diffusivity impact due to the Maxwell nanofluid (graphene/engine oil) flow with motile microorganisms and Joule heating
- Appraising the dielectric properties and the effectiveness of electromagnetic shielding of graphene reinforced silicone rubber nanocomposite
- Synthesis of Ag and Cu nanoparticles by plasma discharge in inorganic salt solutions
- Low-cost and large-scale preparation of ultrafine TiO2@C hybrids for high-performance degradation of methyl orange and formaldehyde under visible light
- Utilization of waste glass with natural pozzolan in the production of self-glazed glass-ceramic materials
- Mechanical performance of date palm fiber-reinforced concrete modified with nano-activated carbon
- Melting point of dried gold nanoparticles prepared with ultrasonic spray pyrolysis and lyophilisation
- Graphene nanofibers: A modern approach towards tailored gypsum composites
- Role of localized magnetic field in vortex generation in tri-hybrid nanofluid flow: A numerical approach
- Intelligent computing for the double-diffusive peristaltic rheology of magneto couple stress nanomaterials
- Bioconvection transport of upper convected Maxwell nanoliquid with gyrotactic microorganism, nonlinear thermal radiation, and chemical reaction
- 3D printing of porous Ti6Al4V bone tissue engineering scaffold and surface anodization preparation of nanotubes to enhance its biological property
- Bioinspired ferromagnetic CoFe2O4 nanoparticles: Potential pharmaceutical and medical applications
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- Photodynamic therapy empowered by nanotechnology for oral and dental science: Progress and perspectives
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Articles in the same Issue
- Research Articles
- Preparation of CdS–Ag2S nanocomposites by ultrasound-assisted UV photolysis treatment and its visible light photocatalysis activity
- Significance of nanoparticle radius and inter-particle spacing toward the radiative water-based alumina nanofluid flow over a rotating disk
- Aptamer-based detection of serotonin based on the rapid in situ synthesis of colorimetric gold nanoparticles
- Investigation of the nucleation and growth behavior of Ti2AlC and Ti3AlC nano-precipitates in TiAl alloys
- Dynamic recrystallization behavior and nucleation mechanism of dual-scale SiCp/A356 composites processed by P/M method
- High mechanical performance of 3-aminopropyl triethoxy silane/epoxy cured in a sandwich construction of 3D carbon felts foam and woven basalt fibers
- Applying solution of spray polyurea elastomer in asphalt binder: Feasibility analysis and DSR study based on the MSCR and LAS tests
- Study on the chronic toxicity and carcinogenicity of iron-based bioabsorbable stents
- Influence of microalloying with B on the microstructure and properties of brazed joints with Ag–Cu–Zn–Sn filler metal
- Thermohydraulic performance of thermal system integrated with twisted turbulator inserts using ternary hybrid nanofluids
- Study of mechanical properties of epoxy/graphene and epoxy/halloysite nanocomposites
- Effects of CaO addition on the CuW composite containing micro- and nano-sized tungsten particles synthesized via aluminothermic coupling with silicothermic reduction
- Cu and Al2O3-based hybrid nanofluid flow through a porous cavity
- Design of functional vancomycin-embedded bio-derived extracellular matrix hydrogels for repairing infectious bone defects
- Study on nanocrystalline coating prepared by electro-spraying 316L metal wire and its corrosion performance
- Axial compression performance of CFST columns reinforced by ultra-high-performance nano-concrete under long-term loading
- Tungsten trioxide nanocomposite for conventional soliton and noise-like pulse generation in anomalous dispersion laser cavity
- Microstructure and electrical contact behavior of the nano-yttria-modified Cu-Al2O3/30Mo/3SiC composite
- Melting rheology in thermally stratified graphene-mineral oil reservoir (third-grade nanofluid) with slip condition
- Re-examination of nonlinear vibration and nonlinear bending of porous sandwich cylindrical panels reinforced by graphene platelets
- Parametric simulation of hybrid nanofluid flow consisting of cobalt ferrite nanoparticles with second-order slip and variable viscosity over an extending surface
- Chitosan-capped silver nanoparticles with potent and selective intrinsic activity against the breast cancer cells
- Multi-core/shell SiO2@Al2O3 nanostructures deposited on Ti3AlC2 to enhance high-temperature stability and microwave absorption properties
- Solution-processed Bi2S3/BiVO4/TiO2 ternary heterojunction photoanode with enhanced photoelectrochemical performance
- Electroporation effect of ZnO nanoarrays under low voltage for water disinfection
- NIR-II window absorbing graphene oxide-coated gold nanorods and graphene quantum dot-coupled gold nanorods for photothermal cancer therapy
- Nonlinear three-dimensional stability characteristics of geometrically imperfect nanoshells under axial compression and surface residual stress
- Investigation of different nanoparticles properties on the thermal conductivity and viscosity of nanofluids by molecular dynamics simulation
- Optimized Cu2O-{100} facet for generation of different reactive oxidative species via peroxymonosulfate activation at specific pH values to efficient acetaminophen removal
- Brownian and thermal diffusivity impact due to the Maxwell nanofluid (graphene/engine oil) flow with motile microorganisms and Joule heating
- Appraising the dielectric properties and the effectiveness of electromagnetic shielding of graphene reinforced silicone rubber nanocomposite
- Synthesis of Ag and Cu nanoparticles by plasma discharge in inorganic salt solutions
- Low-cost and large-scale preparation of ultrafine TiO2@C hybrids for high-performance degradation of methyl orange and formaldehyde under visible light
- Utilization of waste glass with natural pozzolan in the production of self-glazed glass-ceramic materials
- Mechanical performance of date palm fiber-reinforced concrete modified with nano-activated carbon
- Melting point of dried gold nanoparticles prepared with ultrasonic spray pyrolysis and lyophilisation
- Graphene nanofibers: A modern approach towards tailored gypsum composites
- Role of localized magnetic field in vortex generation in tri-hybrid nanofluid flow: A numerical approach
- Intelligent computing for the double-diffusive peristaltic rheology of magneto couple stress nanomaterials
- Bioconvection transport of upper convected Maxwell nanoliquid with gyrotactic microorganism, nonlinear thermal radiation, and chemical reaction
- 3D printing of porous Ti6Al4V bone tissue engineering scaffold and surface anodization preparation of nanotubes to enhance its biological property
- Bioinspired ferromagnetic CoFe2O4 nanoparticles: Potential pharmaceutical and medical applications
- Significance of gyrotactic microorganisms on the MHD tangent hyperbolic nanofluid flow across an elastic slender surface: Numerical analysis
- Performance of polycarboxylate superplasticisers in seawater-blended cement: Effect from chemical structure and nano modification
- Entropy minimization of GO–Ag/KO cross-hybrid nanofluid over a convectively heated surface
- Oxygen plasma assisted room temperature bonding for manufacturing SU-8 polymer micro/nanoscale nozzle
- Performance and mechanism of CO2 reduction by DBD-coupled mesoporous SiO2
- Polyarylene ether nitrile dielectric films modified by HNTs@PDA hybrids for high-temperature resistant organic electronics field
- Exploration of generalized two-phase free convection magnetohydrodynamic flow of dusty tetra-hybrid Casson nanofluid between parallel microplates
- Hygrothermal bending analysis of sandwich nanoplates with FG porous core and piezomagnetic faces via nonlocal strain gradient theory
- Design and optimization of a TiO2/RGO-supported epoxy multilayer microwave absorber by the modified local best particle swarm optimization algorithm
- Mechanical properties and frost resistance of recycled brick aggregate concrete modified by nano-SiO2
- Self-template synthesis of hollow flower-like NiCo2O4 nanoparticles as an efficient bifunctional catalyst for oxygen reduction and oxygen evolution in alkaline media
- High-performance wearable flexible strain sensors based on an AgNWs/rGO/TPU electrospun nanofiber film for monitoring human activities
- High-performance lithium–selenium batteries enabled by nitrogen-doped porous carbon from peanut meal
- Investigating effects of Lorentz forces and convective heating on ternary hybrid nanofluid flow over a curved surface using homotopy analysis method
- Exploring the potential of biogenic magnesium oxide nanoparticles for cytotoxicity: In vitro and in silico studies on HCT116 and HT29 cells and DPPH radical scavenging
- Enhanced visible-light-driven photocatalytic degradation of azo dyes by heteroatom-doped nickel tungstate nanoparticles
- A facile method to synthesize nZVI-doped polypyrrole-based carbon nanotube for Ag(i) removal
- Improved osseointegration of dental titanium implants by TiO2 nanotube arrays with self-assembled recombinant IGF-1 in type 2 diabetes mellitus rat model
- Functionalized SWCNTs@Ag–TiO2 nanocomposites induce ROS-mediated apoptosis and autophagy in liver cancer cells
- Triboelectric nanogenerator based on a water droplet spring with a concave spherical surface for harvesting wave energy and detecting pressure
- A mathematical approach for modeling the blood flow containing nanoparticles by employing the Buongiorno’s model
- Molecular dynamics study on dynamic interlayer friction of graphene and its strain effect
- Induction of apoptosis and autophagy via regulation of AKT and JNK mitogen-activated protein kinase pathways in breast cancer cell lines exposed to gold nanoparticles loaded with TNF-α and combined with doxorubicin
- Effect of PVA fibers on durability of nano-SiO2-reinforced cement-based composites subjected to wet-thermal and chloride salt-coupled environment
- Effect of polyvinyl alcohol fibers on mechanical properties of nano-SiO2-reinforced geopolymer composites under a complex environment
- In vitro studies of titanium dioxide nanoparticles modified with glutathione as a potential drug delivery system
- Comparative investigations of Ag/H2O nanofluid and Ag-CuO/H2O hybrid nanofluid with Darcy-Forchheimer flow over a curved surface
- Study on deformation characteristics of multi-pass continuous drawing of micro copper wire based on crystal plasticity finite element method
- Properties of ultra-high-performance self-compacting fiber-reinforced concrete modified with nanomaterials
- Prediction of lap shear strength of GNP and TiO2/epoxy nanocomposite adhesives
- A novel exploration of how localized magnetic field affects vortex generation of trihybrid nanofluids
- Fabrication and physicochemical characterization of copper oxide–pyrrhotite nanocomposites for the cytotoxic effects on HepG2 cells and the mechanism
- Thermal radiative flow of cross nanofluid due to a stretched cylinder containing microorganisms
- In vitro study of the biphasic calcium phosphate/chitosan hybrid biomaterial scaffold fabricated via solvent casting and evaporation technique for bone regeneration
- Insights into the thermal characteristics and dynamics of stagnant blood conveying titanium oxide, alumina, and silver nanoparticles subject to Lorentz force and internal heating over a curved surface
- Effects of nano-SiO2 additives on carbon fiber-reinforced fly ash–slag geopolymer composites performance: Workability, mechanical properties, and microstructure
- Energy bandgap and thermal characteristics of non-Darcian MHD rotating hybridity nanofluid thin film flow: Nanotechnology application
- Green synthesis and characterization of ginger-extract-based oxali-palladium nanoparticles for colorectal cancer: Downregulation of REG4 and apoptosis induction
- Abnormal evolution of resistivity and microstructure of annealed Ag nanoparticles/Ag–Mo films
- Preparation of water-based dextran-coated Fe3O4 magnetic fluid for magnetic hyperthermia
- Statistical investigations and morphological aspects of cross-rheological material suspended in transportation of alumina, silica, titanium, and ethylene glycol via the Galerkin algorithm
- Effect of CNT film interleaves on the flexural properties and strength after impact of CFRP composites
- Self-assembled nanoscale entities: Preparative process optimization, payload release, and enhanced bioavailability of thymoquinone natural product
- Structure–mechanical property relationships of 3D-printed porous polydimethylsiloxane films
- Nonlinear thermal radiation and the slip effect on a 3D bioconvection flow of the Casson nanofluid in a rotating frame via a homotopy analysis mechanism
- Residual mechanical properties of concrete incorporated with nano supplementary cementitious materials exposed to elevated temperature
- Time-independent three-dimensional flow of a water-based hybrid nanofluid past a Riga plate with slips and convective conditions: A homotopic solution
- Lightweight and high-strength polyarylene ether nitrile-based composites for efficient electromagnetic interference shielding
- Review Articles
- Recycling waste sources into nanocomposites of graphene materials: Overview from an energy-focused perspective
- Hybrid nanofiller reinforcement in thermoset and biothermoset applications: A review
- Current state-of-the-art review of nanotechnology-based therapeutics for viral pandemics: Special attention to COVID-19
- Solid lipid nanoparticles for targeted natural and synthetic drugs delivery in high-incidence cancers, and other diseases: Roles of preparation methods, lipid composition, transitional stability, and release profiles in nanocarriers’ development
- Critical review on experimental and theoretical studies of elastic properties of wurtzite-structured ZnO nanowires
- Polyurea micro-/nano-capsule applications in construction industry: A review
- A comprehensive review and clinical guide to molecular and serological diagnostic tests and future development: In vitro diagnostic testing for COVID-19
- Recent advances in electrocatalytic oxidation of 5-hydroxymethylfurfural to 2,5-furandicarboxylic acid: Mechanism, catalyst, coupling system
- Research progress and prospect of silica-based polymer nanofluids in enhanced oil recovery
- Review of the pharmacokinetics of nanodrugs
- Engineered nanoflowers, nanotrees, nanostars, nanodendrites, and nanoleaves for biomedical applications
- Research progress of biopolymers combined with stem cells in the repair of intrauterine adhesions
- Progress in FEM modeling on mechanical and electromechanical properties of carbon nanotube cement-based composites
- Antifouling induced by surface wettability of poly(dimethyl siloxane) and its nanocomposites
- TiO2 aerogel composite high-efficiency photocatalysts for environmental treatment and hydrogen energy production
- Structural properties of alumina surfaces and their roles in the synthesis of environmentally persistent free radicals (EPFRs)
- Nanoparticles for the potential treatment of Alzheimer’s disease: A physiopathological approach
- Current status of synthesis and consolidation strategies for thermo-resistant nanoalloys and their general applications
- Recent research progress on the stimuli-responsive smart membrane: A review
- Dispersion of carbon nanotubes in aqueous cementitious materials: A review
- Applications of DNA tetrahedron nanostructure in cancer diagnosis and anticancer drugs delivery
- Magnetic nanoparticles in 3D-printed scaffolds for biomedical applications
- An overview of the synthesis of silicon carbide–boron carbide composite powders
- Organolead halide perovskites: Synthetic routes, structural features, and their potential in the development of photovoltaic
- Recent advancements in nanotechnology application on wood and bamboo materials: A review
- Application of aptamer-functionalized nanomaterials in molecular imaging of tumors
- Recent progress on corrosion mechanisms of graphene-reinforced metal matrix composites
- Research progress on preparation, modification, and application of phenolic aerogel
- Application of nanomaterials in early diagnosis of cancer
- Plant mediated-green synthesis of zinc oxide nanoparticles: An insight into biomedical applications
- Recent developments in terahertz quantum cascade lasers for practical applications
- Recent progress in dielectric/metal/dielectric electrodes for foldable light-emitting devices
- Nanocoatings for ballistic applications: A review
- A mini-review on MoS2 membrane for water desalination: Recent development and challenges
- Recent updates in nanotechnological advances for wound healing: A narrative review
- Recent advances in DNA nanomaterials for cancer diagnosis and treatment
- Electrochemical micro- and nanobiosensors for in vivo reactive oxygen/nitrogen species measurement in the brain
- Advances in organic–inorganic nanocomposites for cancer imaging and therapy
- Advancements in aluminum matrix composites reinforced with carbides and graphene: A comprehensive review
- Modification effects of nanosilica on asphalt binders: A review
- Decellularized extracellular matrix as a promising biomaterial for musculoskeletal tissue regeneration
- Review of the sol–gel method in preparing nano TiO2 for advanced oxidation process
- Micro/nano manufacturing aircraft surface with anti-icing and deicing performances: An overview
- Cell type-targeting nanoparticles in treating central nervous system diseases: Challenges and hopes
- An overview of hydrogen production from Al-based materials
- A review of application, modification, and prospect of melamine foam
- A review of the performance of fibre-reinforced composite laminates with carbon nanotubes
- Research on AFM tip-related nanofabrication of two-dimensional materials
- Advances in phase change building materials: An overview
- Development of graphene and graphene quantum dots toward biomedical engineering applications: A review
- Nanoremediation approaches for the mitigation of heavy metal contamination in vegetables: An overview
- Photodynamic therapy empowered by nanotechnology for oral and dental science: Progress and perspectives
- Biosynthesis of metal nanoparticles: Bioreduction and biomineralization
- Current diagnostic and therapeutic approaches for severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) and the role of nanomaterial-based theragnosis in combating the pandemic
- Application of two-dimensional black phosphorus material in wound healing
- Special Issue on Advanced Nanomaterials and Composites for Energy Conversion and Storage - Part I
- Helical fluorinated carbon nanotubes/iron(iii) fluoride hybrid with multilevel transportation channels and rich active sites for lithium/fluorinated carbon primary battery
- The progress of cathode materials in aqueous zinc-ion batteries
- Special Issue on Advanced Nanomaterials for Carbon Capture, Environment and Utilization for Energy Sustainability - Part I
- Effect of polypropylene fiber and nano-silica on the compressive strength and frost resistance of recycled brick aggregate concrete
- Mechanochemical design of nanomaterials for catalytic applications with a benign-by-design focus