摘要Drug resistance is accountable for the inadequate outcome of chemotherapy in clinics.The newly emerging role of nitric oxide(NO)to conquer drug resistance has been recognized as a potential strategy.However,it remains a great challenge to realize targeted delivery as well as accurate release of NO at desired sites.Herein,we developed a PEGylated indocyanine green(mPEG-ICG)integrated nanovesicle system(PIDA)to simultaneously load doxorubicin hydrochloride(DOX·HCl)and the NO donor L-arginine(L-Arg),which can produce NO triggered by NIR light irradiation and exert multimodal therapy to sensitize drug-resistant cancers.Upon 808 nm irradiation,the NO released from PIDA led to a decrease in mitochondrial membrane potential,an increase in ROS and significant ATP depletion in K562/ADR cells,thus inhibiting cell growth and resolving the problem of drug resistance.Consequently,the in vivo experiment on K562/ADR-bearing nude mice indicated that PIDA nanovesicles achieved significant anticancer efficacy with a tumor inhibition rate of 80.8％.Above all,PIDA nanovesicles offer guidance for designing nanoplatforms for drug-resistant cancer treatment.