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Recent process of using nanoparticles in the T cell-based immunometabolic therapy

  • Bingxin Chen , Yangyang Li EMAIL logo und Hui Wang EMAIL logo
Veröffentlicht/Copyright: 23. September 2024
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Nanotechnology Reviews
Aus der Zeitschrift Nanotechnology Reviews Band 13 Heft 1

Abstract

Immunotherapy is currently the main treatment for malignant tumors by activating immune cell. Metabolic reprogramming in tumor microenvironment can greatly affect the function of immune cell, and T cell is the main anti-tumor effector cell. Therefore, the T cell-based immunometabolic therapy can improve clinical efficacy. In T cell-based immunometabolic therapy, regular agents in conventional forms are difficult to achieve the intended efficacy due to poor tumor permeability and low cellular uptake. Nanoparticle-based strategy can serve as the optimal targeted drug delivery system due to co-encapsulation of multiple therapeutic agents and stable loading. Here, we intend to summarize examples of nanoparticles in the T cell-based immunometabolic therapy, and provide a comprehensive and helpful review by covering notable and vital applications of nanotechnology-based strategies for T cell-based immunometabolic therapy.

Keywords: nanoparticles; immunotherapy; T cell; immunometabolism

Abbreviations

ACT

adoptive T-cell therapy

Akt

protein kinase B

ANs

AP-based nanoparticles

AP

amphiphilic poly (γ-glutamic acid)

CA

cis-aconitate

CAR

chimeric antigen receptor

CD

cluster of differentiation

Ce6

Chlorin e6

CRISPR

clustered regularly interspaced short palindromic repeats

DEAP

3-diethylamino propyl isothiocyanate

DHCR7

7-dehydrocholesterol reductase

DPPA-1

d-peptide antagonist of programmed cell death-ligand 1

F/ANs

fenofibrate-loaded fANs

fAP

fluorescent dye-labeled AP

fANs

fAP-based nanoparticles

FDA

Food and Drug Administration

FOXM1

Forkhead box M1

GA

glycolic acid

HRR

homologous recombination repair

ICI

immune checkpoint inhibitors

IDO1

indoleamine 2,3-dioxygenase 1

LA

lactic acid

MMP-2

matrix metalloproteinase-2

MPS

metabolic pathway subtype

mTOR

mammalian target of rapamycin

PAP

prostatic acid phosphatase

PBAE

poly β-amino ester

PD-1

programmed cell death protein 1

PD-L1

programmed cell death-ligand 1

PDT

photodynamic therapy

PI3K

phosphoinositide 3-kinase

PLGA

poly lactic-co-glycolic acid

PLL

ε-poly-l-lysine

PPAR

peroxisome proliferator-activated receptor

PS

photosensitizers

ROS

reactive oxygen species

TCR

T cell receptor

TK

thioketal

TME

tumor microenvironment

TNBC

triple-negative breast cancer

1 Introduction

Cancer is a serious threat to public health [1]. There were an estimated 19.3 million new cancer cases and 10.0 million cancer deaths in 2020. In addition to traditional treatment methods such as surgery, radiotherapy, and chemotherapy, immunotherapy is a rapidly developing new generation of tumor therapy, which has great clinical application prospects [2]. Immunotherapy, mainly including immune checkpoint inhibitors (ICI), adoptive T-cell therapy (ACT), tumor vaccines, and nonspecific immunomodulators, can activate the immune system and eliminate cancer [2–4]. In 2010, the first tumor vaccine (sipuleucel-T) for prostate was approved by the Food and Drug Administration (FDA), which can activate the anti-prostatic acid phosphatase (PAP) immune response [5]. In 2011, the FDA approved the first cytotoxic T lymphocyte-associated antigen-4 monoclonal antibody, ipilimumab, based on the phase III trial (MDX010-20) for metastatic melanoma patients [6,7]. In 2017, the FDA approved the chimeric antigen receptor (CAR) T cell therapy, Yescarta (axicabtagene ciloleucel, cluster of differentiation (CD) 19 CAR T cell) and Kymriah (tisagenlecleucel, CD19 CAR T cell), for the treatment of hematological malignancies [8]. With rapid development, immunotherapy has played an equal role in surgery, chemoradiotherapy, and targeted therapy in tumor treatment, but it still faces challenges [9,10]. In advanced cancer patients, only around 10–40% respond to programmed cell death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) monotherapy, and others are primarily resistant [11]. In melanoma patients sensitive to anti-PD-1/PD-1 monoclonal antibody, nearly 60% would develop acquired resistance [12]. In addition, undesired side effects associated with systemic dissemination are also observed in patients receiving immunotherapy [13–15].

As is known, metabolic reprogramming of the tumor microenvironment (TME) greatly affects the anti-tumor ability of immune cell, which is a key factor affecting the efficacy of immunotherapy (Figure 1) [16–19]. In TME, tumor cell frantically obtains oxygen and nutrients (including glucose, fatty acids, glutamine, etc.) to meet their metabolic needs, and the deficiency of energy sources leads to the suppression of immune cell metabolism [20]. In turn, metabolites, including lactic acid, reactive oxygen species (ROS), and adenosine, can work as immunosuppressive factors [21–26]. Platten et al. found that tumor cell can highly express indoleamine 2,3-dioxygenase 1 (IDO1) to catabolize tryptophan to kynurenine, and this could limit the tryptophan supply to T cell, thereby inhibiting the proliferation and function of T cell [27]. Kynurenine can also activate aromatic hydrocarbon receptors, which results in immunosuppression [28–30]. Several small molecule inhibitors targeting IDO1 have entered clinical trials, but whether IDO1 inhibitors will bring clinical utility remains unclear [31]. Therefore, an imminent challenge for T cell-based immunometabolic therapy is to develop effective strategies to realize the potential for clinical application [32–36].

Figure 1 Metabolic competition between tumor cell and CD8+ T cell. In the TME, tumor cell takes up a large amount of metabolic raw materials and accumulate metabolic wastes, leading to metabolic disorders of CD8+ T cell.
Figure 1

Metabolic competition between tumor cell and CD8+ T cell. In the TME, tumor cell takes up a large amount of metabolic raw materials and accumulate metabolic wastes, leading to metabolic disorders of CD8+ T cell.

However, the complexity of the TME has been found to increase difficulty of developing T cell-based immunometabolic therapy [37]. Lack of selectivity for tumor cells lead to inefficient drug delivery in T cell-based immunometabolic therapy, which limit clinical application [37]. In addition, nontumor-specific immune activation led to systemic side effects [37]. To implement T cell-based immunometabolic therapy, nanoparticles can work as the scientific and practical drug delivery systems based on their biocompatibility and ability to improve drug circulation and targeting [38,39]. Herein, we systematically introduce these immunotherapies, and focus on various applications of nanoparticles in T cell-based immunometabolic therapy.

2 Application and development of nanoparticles

Nanoparticles can be divided into organic nanoparticles (including lipid nanoparticles, polymer nanoparticles, etc.) and inorganic nanoparticles (including metal nanoparticles, inorganic non-metallic nanomaterials, etc.), and exhibit many advantages in drug delivery, including stable loading, specific delivery, improved bioavailability, and co-encapsulation of multiple therapeutic agents [38,39]. Since the first nanomedicine was approved by the FDA in 1995, several nanomedicines have been applied in cancer treatment [40–43]. As immunotherapy plays an increasingly important role in tumor treatment, nanotechnology has emerged as an attractive and effective strategy to enhance anti-tumor immune response [44].

2.1 Nanoparticles that modulate T-cell metabolism

As is known, there exists intense nutritional competition between tumor cell and immune cell [20–24]. In TME, naive T cell mainly depends on oxidative phosphorylation, but upon activation, T cell switches metabolism into aerobic glycolysis via the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway to support the differentiation into effector T cell [45–48]. To upregulate the anti-tumor activity of T cell, metabolism-modulating drugs can be applied to inhibit tumor cell metabolism or promote T cell nutrient uptake [16,17]. Nanoparticles can work as the optimal targeted drug delivery system of metabolism-modulating drugs [40,41].

Kim et al. reported an application of nanoparticle-mediated lipid metabolic reprogramming in T cell [49]. Based on carbodiimide crosslinking reaction, grafting phenylalanine ethyl ester with poly (γ-glutamic acid) synthesized amphiphilic poly (γ-glutamic acid) (AP). Fenofibrate was packaged in AP-based nanoparticles (ANs) or fluorescent dye-labeled AP-based nanoparticles (fANs), and then fenofibrate-loaded fANs (F/ANs) were obtained. The surface of F/ANs was modified with anti-CD3ef(ab’)2 fragment to yield aCD3/F/ANs and achieve targeted delivery of T cell (Figure 2a and b). Fenofibrate can up-regulate expression levels of peroxisome proliferator-activated receptor (PPAR)-α and fatty acid translocase CD36. After treating with aCD3/F/ANs, the expression of PPARα and CD36 on cell membrane was increased in T cell. This resulted in a 3.1-fold increase in lipid uptake by T cell treated with aCD3/F/ANs, thus affecting the survival and proliferation of T cell (Figure 2c and d). Treatment with aCD3/F/ANs significantly enhanced the CD8+ T cell, as well as secretion of IFN-γ and granzyme B. The anti-cancer effect of T cell is limited, mainly because of glucose deficiency in TME. In this work, aCD3/F/AN can reprogram the mitochondrial lipid metabolism of T cell in glucose deficiency in TME with low glucose, and enhance the survival and effect function of T cell. These results provided strong evidence that nanoparticle-based drug delivery systems displayed great potential in the T cell-based immunometabolic therapy.

Figure 2 Application of nanoparticle-mediated lipid metabolic reprogramming in T cell. (a) Schematic illustration of the nanoparticle. (b) Morphology of aCD3/F/ANs. Scale bar: 200 nm. After treatment in different groups, the association of fluorescent lipid with T cell was determined by flow cytometry (c) and expressed as mean fluorescence intensity (d) (***P  <  0.001). Reproduced from Ref. [49]. Copyright 2021, Springer Nature.
Figure 2

Application of nanoparticle-mediated lipid metabolic reprogramming in T cell. (a) Schematic illustration of the nanoparticle. (b) Morphology of aCD3/F/ANs. Scale bar: 200 nm. After treatment in different groups, the association of fluorescent lipid with T cell was determined by flow cytometry (c) and expressed as mean fluorescence intensity (d) (***P  <  0.001). Reproduced from Ref. [49]. Copyright 2021, Springer Nature.

2.2 Nanoparticles that combine T-cell metabolism and ICIs

ICIs can restore effective T cell function by blocking the immune checkpoints, and are widely used in tumor treatment [50,51]. According to the metabolic characteristics, Gong et al. divided triple-negative breast cancer (TNBC) into three heterogeneous metabolic pathway subtype (MPS), and anti-LDH therapy can enhance tumor response to anti-PD-1 monoclonal antibody in MPS2 (the glycolytic subtype with upregulated carbohydrate and nucleotide metabolism) [52]. Therefore, the metabolic reprogramming in TME significantly affects the efficacy of ICIs. However, the optimal T cell-based immunometabolic therapy to undergo treatment at low doses and reduce related adverse events remains to be explored.

Facing these challenges, Cheng et al. reported a therapeutic peptide assembling nanoparticle for dual-targeted cancer immunotherapy, namely NLG919@DEAP-DPPA-1-Scr [53], which contain amphiphilic peptide and the IDO1 inhibitor (NLG919). The amphiphilic peptide was designed to consist of a functional 3-diethylamino propyl isothiocyanate (DEAP) molecule, a peptide substrate of matrix metalloproteinase-2 (MMP-2), and a short d-peptide antagonist of programmed cell death-ligand 1 (DPPA-1) (Figure 3a). When in the weakly acidic environment, protonated DEAP and cleavage by MMP-2 result in the local release of DPPA-1 and NLG919 in tumor region. In the tumor-bearing mice, this sequentially responsive therapeutic peptide assembling nanoparticles can simultaneously block immune checkpoints and tryptophan metabolism, thereby promoting the activation of cytotoxic T lymphocytes, slowing melanoma growth and improving survival rate (Figure 3b and c). These studies successfully incorporated nanoparticles into T cell-based immunometabolic therapy and demonstrated the important potential of nanoparticles.

Figure 3 Therapeutic peptide assembling nanoparticle for dual-targeted cancer immunotherapy. (a) Composition of DEAP-DPPA-1. (b) Inhibitory effect of NLG919 and NLG919@DEAP-DPPA-1 nanoparticles on IDO enzyme activity was evaluated by examining the amount of kynurenine (Kyn) in the B16-F10 cell medium. (c) Survival curve of mice treated with various formulations (n = 10). Treatment groups: 1, DEAP-DPPA-1-Scr; 2, NLG919; 3, NLG919@DEAP-DPPA-1-Scr; 4, DEAP-DPPA-1; 5, NLG919@DEAP-DPPA-1. Reproduced from Ref. [53]. Copyright 2018, American Chemical Society.
Figure 3

Therapeutic peptide assembling nanoparticle for dual-targeted cancer immunotherapy. (a) Composition of DEAP-DPPA-1. (b) Inhibitory effect of NLG919 and NLG919@DEAP-DPPA-1 nanoparticles on IDO enzyme activity was evaluated by examining the amount of kynurenine (Kyn) in the B16-F10 cell medium. (c) Survival curve of mice treated with various formulations (n = 10). Treatment groups: 1, DEAP-DPPA-1-Scr; 2, NLG919; 3, NLG919@DEAP-DPPA-1-Scr; 4, DEAP-DPPA-1; 5, NLG919@DEAP-DPPA-1. Reproduced from Ref. [53]. Copyright 2018, American Chemical Society.

According to the high ROS level in TME, Wan et al. designed a ROS-sensitive nanoparticle, which loaded siFGL1 and siPD-L1 [54]. Thioketal (TK), which is ROS-sensitive, and cis-aconitate (CA) form CA-PLL-TK, with the skeleton of the polycationic material ε-poly-l-lysine (PLL). Then siFGL1 and siPD-L1 were loaded through electrostatic adsorption, and were administered with iRGD. After a combination of CA and hydrogen protons, the conformation of the nanoparticle was changed. Then the ROS resulted in the disruption of the nanoparticle structure and the release of siFGL1 and siPD-L1 (Figure 4a–d). The expression of FGL1 and PD-L1 was downregulated after co-incubation with CPT-NPs/siFGL1/siPD-L1. After the treatment of CPT-NPs/siFGL1/siPD-L1 + iRGD in tumor-bearing C57BL/6 mice, the volume and weight of the tumor decreased, the levels of IL-2, IFN-γ, and TNF-α were elevated, and the number of CD4+ T cell and CD8+ T cell increased. The results suggested that tumor-penetrating peptide iRGD and ROS-responsive nanoparticles can promote the delivery efficiency. To sum up, nanoparticles can load metabolic regulatory drugs and ICIs, and increase clinical efficacy.

Figure 4 ROS-sensitive nanoparticle loading siFGL1 and siPD-L1. (a) and (b) Size distribution of CPT-NPs in different pH values. (c) Zeta potential changes of CPT-NPs. (d) TEM images of CPT-NPs. Reproduced from Ref. [54]. Copyright 2021, Elsevier.
Figure 4

ROS-sensitive nanoparticle loading siFGL1 and siPD-L1. (a) and (b) Size distribution of CPT-NPs in different pH values. (c) Zeta potential changes of CPT-NPs. (d) TEM images of CPT-NPs. Reproduced from Ref. [54]. Copyright 2021, Elsevier.

2.3 Nanoparticles that combine T-cell metabolism and ACT

ACT has achieved great success in the treatment of malignant tumors, especially hematological malignancies [55,56]. Adoptive T cell from donor would be reinfused back to the patient to attack abnormal cell after experiencing ex vivo expansion and engineering [56]. However, ACT still has significant limitations that must be addressed, including post-transfer T cell exhaustion and death, limited efficacy in solid tumors, and severe side effects [57,58].

Previous studies have reported that the function of T cell needs the cholesterol on the cell membrane to aggregate the T cell receptor (TCR) and form immune synapses [59–61]. Avasimibe, working as an inhibitor of cholesterol esterase acetyl CoA acetyltransferase 1, can elevate cholesterol concentrations and facilitate TCR clustering, to upregulate the anti-tumor ability of T cell [62]. Hao et al. proposed a new strategy to combine the lipid metabolism-modulating drug Avasimibe with adoptive T cell for solid tumor therapy [63]. This novel T cell surface anchoring technology anchored the lipid on the T cell membrane through hydrophobic force, and then coupled the lipid and the drug liposome on the T cell membrane through a click reaction (Figure 5a) [63]. In this process, the researchers constructed bicyclo[6.1.0]nonyne (BCN)-modified Au nanoparticles (BCN-Au), which enabled the drug to be attached on the surface of T cell (Figure 5b). After avasimibe was loaded on the surface of T cell, the physiological function of the T cell was not disturbed. Engineered T cell can increase the cholesterol level of the T cell membrane through the dual effects of “autocrine and paracrine,” to promote the rapid aggregation of TCRs and increase the sustained activation of T cell (Figure 5c). Treatment with surface anchor-engineered T cell shows excellent efficacy in in vivo experiments, and three of the five mice completely eradicated glioblastoma [63]. Here, liposomal Avathimide is clicked on the surface of T cell through lipid insertion, without interfering with the physiological function of T cell. This combination strategy results in good curative effects and few toxic side effects.

Figure 5 Nanoparticle that combines the lipid metabolism-modulating drug Avasimibe with adoptive T cell. (a) Structures of T-Tre/BCN-Lipo. (b) SEM of a T-Tre/BCN-Au cell and a T cell. Red arrows indicate BCN-Au nanoparticles. White scale bar, 1 μm. Black scale bar, 500 nm. (c) Quantification of plasma membrane cholesterol content in CD8+ T cell. Reproduced from Ref. [63]. Copyright 2020, American Association for the Advancement of Science.
Figure 5

Nanoparticle that combines the lipid metabolism-modulating drug Avasimibe with adoptive T cell. (a) Structures of T-Tre/BCN-Lipo. (b) SEM of a T-Tre/BCN-Au cell and a T cell. Red arrows indicate BCN-Au nanoparticles. White scale bar, 1 μm. Black scale bar, 500 nm. (c) Quantification of plasma membrane cholesterol content in CD8+ T cell. Reproduced from Ref. [63]. Copyright 2020, American Association for the Advancement of Science.

2.4 Nanoparticles that combine T-cell metabolism and other immune-related therapies

Nanoparticles are also used in combination with T-cell metabolism and other immune-related therapies. Photodynamic therapy (PDT) relies on photosensitizers (PS) to absorb light energy and convert oxygen into cytotoxic ROS to directly kill tumor cell [64,65]. However, the hypoxic state of the TME always affects the efficacy of PDT [66]. Xing et al. reported the fluorinated polymeric nanoparticles (PF-PEG NPs) with PS Chlorin e6 (Ce6) and IDO1 inhibitor NLG919 in the hydrophobic core (Figure 6a) [67]. These nanoparticles possess a better oxygen-carrying and longer oxygen retention ability, which can solve the hypoxic state of the TME (Figure 6b and c). Meanwhile, the co-encapsulation of NLG919 and PS can improve T cell infiltration, as well as IFN-γ positive CD8+ T cell, and inhibit tumor growth. In this study, a multi-functional nanoplatform constructed with oxygen-enriched fluorinated polymer nanoparticles with Chlorin e6 and NLG919 was developed to realize the combination of IDO inhibitor and PDT. This work is a successful model of the achievements of nanoparticles in T cell-based immunometabolic therapy and provides clinical benefits in cancer treatment.

Figure 6 Nanoparticle loading Ce6 and NLG919. (a) TEM image of PF-PEG@Ce6@NLG919 NPs. (b) Dissolved oxygen release curves of PF-PEG NPs, PA-PEG NPs, and PBS. (c) Oxygen dissolution of PBS, Free Ce6, and PF-PEG@Ce6 NPs showed a 3-fold enhancement of PF-PEG@Ce6 compared with Ce6. Reproduced from Ref. [67]. Copyright 2019, Elsevier.
Figure 6

Nanoparticle loading Ce6 and NLG919. (a) TEM image of PF-PEG@Ce6@NLG919 NPs. (b) Dissolved oxygen release curves of PF-PEG NPs, PA-PEG NPs, and PBS. (c) Oxygen dissolution of PBS, Free Ce6, and PF-PEG@Ce6 NPs showed a 3-fold enhancement of PF-PEG@Ce6 compared with Ce6. Reproduced from Ref. [67]. Copyright 2019, Elsevier.

3 Clinical application of nanoparticles

With the rapid development, nanoparticles play an increasingly important role in the treatment of malignant tumors [68]. Nanoparticles can change their sizes, shapes, charges, and surface modifications to deliver molecules, thereby improving therapeutic efficacy and reducing side effects, for example, improving vascular dynamics by changing the size and shape of nanoparticles, or avoiding phagocyte absorption using biomimetic membranes [69]. Nanoparticles can also complete the targeted delivery by adding targeted ligands, which is difficult for other traditional delivery systems [70]. The uptake of nanoparticles in tumors is achieved through enhanced permeability and retention effect and the active recognition of targeted ligands by receptors over-expressed at pathological sites [71]. But the clinical transformation of nanoparticles still faces many challenges, including insufficient distribution and accumulation of therapeutic drugs, as well as off-target toxicity in the liver and spleen, which may be caused by non-specific removal by the reticuloendothelial system. The production of nanoparticles usually requires a more complex synthesis process than traditional drugs, which makes it difficult to be produced on a large scale and ensure quality control [71]. Currently, common nanoparticles include polymer nanoparticles, lipidic nanocarriers, protein complexes, metal organic skeleton complexes, and inorganic nanoparticles.

Poly lactic-co-glycolic acid (PLGA) is an FDA approved biodegradable polymer nanoparticle [72]. PLGA molecule contains lactic acid (LA) and glycolic acid (GA), and the LA/GA ratio can affect the stability and degradation time of PLGA [73]. PLGA has good biocompatibility and biodegradability, controllable degradation rate, but its loading capacity is low, especially for hydrophilic and/or amphiphilic small molecules [74].

Liposomes are spherical lipidic nanocarriers composed of a lipid bilayer with phospholipids and cholesterol, forming an amphipathic nano/micro-particle [75], which have been used as an important nano-delivery system [76]. Abumanhal-Masarweh et al. constructed liposomes loaded with sodium bicarbonate, and combined them with doxorubicin to treat TNBC (Figure 7a and b) [77]. The combination therapy can modulate the tumor pH (Figure 7c), promote the infiltration of immune cell, T cell, B cell and macrophage in TME, and inhibit tumor progression [77]. Liposomes are one of the most successful nanodelivery systems, and a variety of liposomes have been approved by FDA [75,76]. Therefore, liposomes have a great application prospect in T cell-based immunometabolic therapy.

Figure 7 Liposomes loaded with sodium bicarbonate and doxorubicin. (a) Liposomes encapsulating sodium bicarbonate were constructed of hydrogenated soybean phosphatidylcholine, cholesterol, and PEG-distearoyl-phosphoethanolamine. (b) Schematic diagram of the effect of pH on the efficacy of doxorubicin. (c) The pH value was 7.38 ± 0.04 in the liposomal bicarbonate-treated group, 7.13 ± 0.06 in the untreated tumor, and 7.46 ± 0.01 in healthy mammary fat pad. Reproduced from Ref. [77]. Copyright 2019, Elsevier.
Figure 7

Liposomes loaded with sodium bicarbonate and doxorubicin. (a) Liposomes encapsulating sodium bicarbonate were constructed of hydrogenated soybean phosphatidylcholine, cholesterol, and PEG-distearoyl-phosphoethanolamine. (b) Schematic diagram of the effect of pH on the efficacy of doxorubicin. (c) The pH value was 7.38 ± 0.04 in the liposomal bicarbonate-treated group, 7.13 ± 0.06 in the untreated tumor, and 7.46 ± 0.01 in healthy mammary fat pad. Reproduced from Ref. [77]. Copyright 2019, Elsevier.

Inorganic nanoparticles can obtain appropriate dispersion through surface modification, and additional functions can be performed [78]. For example, capsule containing gold nanoshells can respond to near-infrared light to facilitate on-demand drug release [79]. Typical inorganic nanoparticles include gold, iron oxide, silver, or silica. The main reasons for the limited clinical application of inorganic nanoparticles are low solubility and toxicity [78].

Due to the unique properties, the application of nanoparticles has been gradually explored in T cell-based immunometabolic therapy. Table 1 shows various representative nanoparticles that combined T cell metabolism and T cell-based immunotherapy. Despite the enormous potential of nanoparticles in cancer therapy, they are in the relatively early stages of clinical applications.

Table 1

Representative nanoparticles in the T cell-based immunometabolic therapy

Delivery system Combined therapy Drug Metabolite Tumor type Ref.
aCD3/F/AN Activation of T cells Fenofibrate Lipid Melanoma [49]
NLG919@DEAP-DPPA-1-Scr ICI Amphiphilic peptide, NLG919 Tryptophan Melanoma [53]
CPT-NPs/siFGL1/siPD-L1 + iRGD ICI siFGL1, siPD-L1 ROS Lung cancer [54]
T-Tre/BCN-Lipo ACT Avasimibe Cholesterol Glioblastoma [63]
PF-PEG@Ce6@NLG919 Other therapy NLG919, photosensitizers Tryptophan Breast cancer and cervical cancer [67]
Liposomal doxorubicin plus liposomal bicarbonate Other therapy Sodium bicarbonate PH Breast cancer [77]

4 Future perspectives

Immunotherapy aims to activate immune cells to kill and eliminate tumor cells, and metabolic reprogramming in TME can induce immune cell dysfunction and decrease the response to immunotherapy. In the last few years, tremendous advances have been made in T cell-based immunometabolic therapy, but the complexity of the TME increases the difficulty of drug delivery. To implement T cell-based immunometabolic therapy, nanoparticles can be used as a scientific and practical drug delivery system. In this review, the recent process of using nanoparticles in the T cell-based immunometabolic therapy is analyzed and prospected.

Nanoparticles possess excellent performance in targeted drug delivery, stimulated reactive drug release, and delivery of combination drugs. With the assistance of nanoparticles, researchers developed new therapies to regulate metabolism in combination with immunotherapy. We discussed several representative nanoparticles in the T cell-based immunometabolic therapy, and found that they all demonstrated excellent efficacy. Meanwhile, we are aware that some issues remain to be addressed to achieve clinical translation: (1) research on metabolic reprogramming provides theoretical basis, (2) nanoparticles need to be carefully designed for safety requirements, and (3) targeted delivery is helpful to improve effectiveness (Figure 8).

Figure 8 Future perspective of nanoparticles in the T cell-based immunometabolic therapy. The figure is drawn by Figdraw.
Figure 8

Future perspective of nanoparticles in the T cell-based immunometabolic therapy. The figure is drawn by Figdraw.

First, the influence of metabolic reprogramming on immunotherapy and the relative mechanism are complex and require further exploration. The metabolism of immune cells and cancer cells in TME is interdependent. Cancer cells consume nutrients and produce immunosuppressive metabolites, thus promoting malignant progression. We reported that in cervical cancer, 7-dehydrocholesterol reductase (DHCR7), an enzyme that catalyzes the last step of cholesterol synthesis, was upregulated and closely related to the prognosis [80]. DHCR7 can promote lymph node metastasis in cervical cancer through cholesterol reprogramming in TME [80]. However, many other effects and mechanisms of metabolic reprogramming remain unclear. In-depth study can provide more theoretical basis for using nanoparticles in the T cell-based immunometabolic therapy.

Second, the safety concern of nanoparticles is one of the core issues in the application of nanoparticles in the T cell-based immunometabolic therapy. The trials of nanoparticles in immunotherapy have been carried out in large numbers over recent years. In sharp contrast, very few nanoparticles have been used clinically so far. Nanoparticles are accumulated in the lungs, spleen, kidney, liver and heart, and are difficult to remove, which raises concerns about the safety of nanoparticles. The chemical composition, size, shape, specific surface area, and surface charge of nanoparticles need to be carefully designed for safety requirements, and directly affect the scale and difficulty of nanoparticle production.

Third, the distribution of nanoparticles can directly affect their effectiveness in T cell-based immunometabolic therapy. Metabolic competition in the TME can also affect the delivery of nanoparticles. Therefore, how to achieve targeted delivery and controlled release performance is one of the current research difficulties. In order to solve these difficulties, we can design the nanoparticles based on the metabolic characteristics of TME, such as hypoxia, acidity, and high ROS. The targeted modification of nanoparticles can also be achieved using ligands or antibodies with specific recognition capabilities to improve the distribution and enrichment of nanoparticles in vivo. Imaging technology can track the dynamic distribution and enrichment of nanoparticles in the T cell-based immunometabolic therapy.

As this review indicates, T cell-based immunometabolic therapy holds great promise, and nanodelivery system can solve the problems of pharmacokinetic inconsistencies and bioutilization difficulties. There are still many difficulties that need to be overcome in the clinical translation of nanoparticles in T cell-based immunometabolic therapy.

  1. Funding information: This work was funded by Key R&D Program of Zhejiang (No. 2022C03013), Zhejiang Province Natural Science Funds Grant (No. LQ23H160033), and Zhejiang Medical and Health Science and Technology program (No. 2024KY116).

  2. Author contributions: Bingxin Chen: conceptualization, resources, writing – review and editing, visualization, supervision, project administration; Yangyang Li: conceptualization, literature analysis, figure design, writing – original draft, review and edition. Hui Wang: conceptualization, writing – review and editing, visualization. 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.

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Received: 2023-07-17
Revised: 2024-03-31
Accepted: 2024-07-11
Published Online: 2024-09-23

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

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

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  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-2024-0072
Schlagwörter für diesen Artikel
nanoparticles; immunotherapy; T cell; immunometabolism
Creative Commons
BY 4.0

Artikel in diesem Heft

  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
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