Drug-independent NADPH-consuming micelles collaborate with ROS-generator for cascade ferroptosis amplification by impairing redox homeostasis.

ABSTRACT: Ferroptosis as promising antitumor therapy strategy could be comprised by intracellular antioxidants, especially GSH and thioredoxin (Trx). They are both cofactors of Gpx4, the enzyme catalyzing the production of lipid peroxides to relieve oxidative stress, which drives the acquired ferroptosis resistance in tumors. Herein, the NADPH-consuming micelles are specially designed, which could collaborate with the ROS generating photodynamics therapy (PDT) by depleting intracellular GSH and Trx under hypoxia condition, resulting in ruined redox homeostasis and the final cascade amplified ferroptosis. The tailored micelle was briefly prepared by conjugating hypoxia-sensitive segment p-nitrobenzyl chloroformate (PNZ-Cl) to the hydrophilic chitosan (CS), the resulting micelle was further modified w

SUBMITTER: Yu F 

PROVIDER: S-EPMC9860483 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature