Recent advances in redox-responsive nanoparticles for combined cancer therapy

Sun, Wen; Yang, Yanjun

doi:10.1039/d2na00222a

Cited by 37 publications

(17 citation statements)

References 129 publications

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“…Redox‐responsive self‐assembled polymeric nanocarriers are currently at the preclinical stage of evaluation and there remain several problems necessitating resolution [32] . This accordingly highlights the need for a range of different approaches that could potentially be adopted to enhance the interaction of these carriers with target cell receptors, rather than simply facilitating the EPR effect.…”

Section: Discussionmentioning

confidence: 99%

“…Redox-responsive self-assembled polymeric nanocarriers are currently at the preclinical stage of evaluation and there remain several problems necessitating resolution. [32] This accordingly highlights the need for a range of different approaches that could potentially be adopted to enhance the interaction of these carriers with target cell receptors, rather than simply facilitating the EPR effect. Further in-depth studies are required to elucidate the underlying metabolic pathways and to assess any potential long-term side effects attributable to the administration of polymeric nanocarriers for targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

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Controlling Morphologies of Redox‐Responsive Polymeric Nanocarriers for a Smart Drug Delivery System

Lee

Kwon

2023

Chemistry A European J

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Redox‐responsive nanocarriers using disulfides or thiols have received considerable attention owing to the higher levels of glutathione (GSH) in cancer cells than those in extracellular fluids. Nevertheless, the normal‐to‐cancer‐cell selectivity of these nanocarriers has not yet been clarified. Nanocarriers exhibit different cytotoxicities depending on the morphologies they adopt under the redox‐active conditions typically existing in cancerous cells. Therefore, not only GSH levels but also reactive oxygen species (ROS) levels and other complex cancerous cell conditions must be considered for the development of smart drug delivery systems. In this article, we review the structural design of redox‐responsive polymers that exhibit different morphological changes in environments akin to cancerous cells (e. g., GSH‐ and ROS‐abundant conditions). In addition, we propose a molecular design for the spatiotemporal control of nanocarrier morphology depending on the levels of both GSH and ROS upon photoirradiation to increase the cytotoxicity difference between normal and cancer cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Controlling Morphologies of Redox‐Responsive Polymeric Nanocarriers for a Smart Drug Delivery System

Lee

Kwon

2023

Chemistry A European J

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“…Although surgery, radiotherapy, chemotherapy, immunotherapy, and corresponding comprehensive treatment tactics were coming up successively during the past few decades, chemotherapy was always one of the most commonly used methods in clinical practice. To overcome the inherent defects of conventional hydrophobic anti-cancer drugs, various polymer-based envelope materials were developed one after another to improve the solubility of hydrophobic drugs, enhance the treatment outcome and reduce the side effects. − Because of the sensitive phase transition generated by external environments (including pH, temperature, light, and redox substances), stimuli-responsive polymers had attracted wide attention of scholars around the world. − …”

Section: Introductionmentioning

confidence: 99%

Construction of Actively Targeted and High Drug Content Polyprodrug Amphiphiles to Perform Synergistic Chemo–Photo-Anti-Tumor Therapy and Immune-Activated Investigation

et al. 2023

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Chemotherapy is one of the most employed strategies in clinical treatment of cancer, but the low content of drug molecules caused by the inadequate accumulation of drug carriers in the lesion locations has an adverse impact on the therapeutic effect. To solve this issue, a kind of high drug content prodrug monomers with topological structures of AB2 and AB3 were designed and utilized to construct a series of polyprodrug amphiphiles, P[GMA(-l-RGD/-PEG)-CPT n ] (n = 2 or 3), with both targeting peptides (l-RGD) and high drug content. Depending on the structure of prodrug monomers, the content of drug molecules could be achieved as high as 60 wt % (n = 2) and 65 wt % (n = 3), respectively. These polyprodrug amphiphiles could self-assemble with photothermal conversion reagents (IR780) in water to form spherical nanoparticles, which could expose original hidden l-RGD through the removal of hydrophilic PEG coronas under the trigger of a tumor microenvironment and thus promote the endocytosis of nanoparticles. Once in the presence of intracellular glutathione (GSH), high content drug molecules could be efficiently released by a cascade amplification reaction to kill cancer cells, this process could be further enhanced by the synergistic effect of local hyperthermia induced by near-infrared light irradiation. The results from in vitro simulation and in vivo mouse solid tumor models showed that these nanoreagents had a highly inhibitory effect on the tumor. Not only that, the immune response after chemical–optical synergistic therapy was also systematically conducted, the results demonstrated that the maturation of dendritic cells and proliferation of T cells could be successfully activated, accompanied by the increase of high mobility group protein B1 and decrease of immunosuppressive regulatory T cells. We believe this proof-of-concept could effectively solve the bottleneck problem in chemotherapy and provide a continuous immune protection to the body after anti-tumor treatment.

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“…In recent years, the design of ROS-responsive nanoparticles as a drug carrier has become a promising research area. − ROS is overproduced in a wide range of pathological microenvironments, such as the terrain of cancer, diabetes, inflammatory, cardiovascular and degenerative diseases, distinguishing the pathological area from the surrounding normal environment. , As a consequence, ROS-responsive nanoparticles are promising for site-specifically delivering cargo drug molecules to pathological sites by targeting peroxidation microenvironment and exhibit potential biomedical applications in many aspects . As stated above, oxidative stress is a critical factor in the NAFLD pathogenesis that mediates liver injury.…”

Section: Introductionmentioning

confidence: 99%

Engineered Fenofibrate as Oxidation-Sensitive Nanoparticles with ROS Scavenging and PPARα-Activating Bioactivity to Ameliorate Nonalcoholic Fatty Liver Disease

Huang

Peng

et al. 2022

Mol. Pharmaceutics

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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in western countries and China. Fenofibrate (FNB) can activate peroxisome proliferator-activated receptor α (PPARα) to increase fatty acid oxidation and ameliorate NAFLD. However, the application of FNB is limited in clinic due to its poor water solubility and low oral bioavailability. In this study, FNB-loaded nanoparticles (FNB-NP) based on a reactive oxygen species (ROS)-responsive peroxalate ester derived from vitamin E (OVE) and an amphiphilic conjugate 1,2-distearoyl-sn-glycerol-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE-PEG) were developed to enhance the preventive effects of FNB against NAFLD. In in vitro studies, FNB-NP displayed a high encapsulation efficiency of 97.25 ± 0.6% and a drug loading efficiency of 29.67 ± 0.1%, with a size of 197.0 ± 0.2 nm. FNB released from FNB-NP was dramatically accelerated in the medium with high H2O2 concentrations. Moreover, FNB-NP exhibited well storage stability and plasma stability. In pharmacokinetic (PK) studies, FNB-NP, compared with FNB crude drug, significantly increased the AUC0→t and AUC0→∞ of the plasma FNB acid by 3.3- and 3.4-fold, respectively. In pharmacodynamics (PD) studies, compared with an equal dose of FNB crude drug, FNB-NP more significantly reduced hepatic lipid deposition via facilitating FNB release in the liver and further upregulating PPARα expression in NAFLD mice. Meanwhile, oxidative stress in NAFLD was significantly suppressed after FNB-NP administration, suggesting that OVE plays a synergistic effect on antioxidation. Therefore, ROS-sensitive FNB delivery formulations FNB-NP enhance the preventive effects of FNB against NAFLD and could be further studied as a promising drug for the treatment of NAFLD in clinic.

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Recent advances in redox-responsive nanoparticles for combined cancer therapy

Abstract: The combination of multiple therapeutic modalities has attracted an increasingly attention, which achieve better therapeutic effects through different treatment mechanisms. However, traditional small molecule agents are non-specific to the tumor...

Cited by 37 publications

References 129 publications

Controlling Morphologies of Redox‐Responsive Polymeric Nanocarriers for a Smart Drug Delivery System

Controlling Morphologies of Redox‐Responsive Polymeric Nanocarriers for a Smart Drug Delivery System

Construction of Actively Targeted and High Drug Content Polyprodrug Amphiphiles to Perform Synergistic Chemo–Photo-Anti-Tumor Therapy and Immune-Activated Investigation

Engineered Fenofibrate as Oxidation-Sensitive Nanoparticles with ROS Scavenging and PPARα-Activating Bioactivity to Ameliorate Nonalcoholic Fatty Liver Disease

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