Glutathione-depleting polyprodrug nanoparticle for enhanced photodynamic therapy and cascaded locoregional chemotherapy
Journal of Colloid and Interface Science(2024)
摘要
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.
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关键词
Cancer therapy,Reactive oxygen species,Polyprodrug,Triggered drug release,Nanomedicine
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