1. Glutathione-depleting polyprodrug nanoparticle for enhanced photodynamic therapy and cascaded locoregional chemotherapy.
- Author
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Zhang X, Zhang X, Chen S, Liu Y, Cao C, Cheng G, and Wang S
- Subjects
- Humans, Animals, Photosensitizing Agents chemistry, Photosensitizing Agents pharmacology, Photosensitizing Agents administration & dosage, Mice, Drug Screening Assays, Antitumor, Particle Size, Hydrogen Peroxide metabolism, Cell Survival drug effects, Cell Proliferation drug effects, Surface Properties, Cell Line, Tumor, Drug Liberation, Tumor Microenvironment drug effects, Indolequinones, Photochemotherapy, Glutathione metabolism, Glutathione chemistry, Nanoparticles chemistry, Prodrugs pharmacology, Prodrugs chemistry, Reactive Oxygen Species metabolism, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology
- Abstract
Nanomedicines that combine reactive oxygen species (ROS)-responsive polyprodrug and photodynamic therapy have shown great potential for improving treatment efficacy. However, the consumption of ROS by overexpressed glutathione in tumor cells is a major obstacle for achieving effective ROS amplification and prodrug activation. Herein, we report a polyprodrug-based nanoparticle that can realize ROS amplification and cascaded drug release. The nanoparticle can respond to the high level of hydrogen peroxide in tumor microenvironment, achieving self-destruction and release of quinone methide. The quinone methide depletes intracellular glutathione and thus decreases the antioxidant capacity of cancer cells. Under laser irradiation, a large amount of ROS will be generated to induce cell damage and prodrug activation. Therefore, the glutathione-depleting polyprodrug nanoparticles can efficiently inhibit tumor growth by enhanced photodynamic therapy and cascaded locoregional chemotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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