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作者： Weixi Jiang Jingxue Wang Li Chen Xiaoling Qiu Chier Du Hongjin An Xun Guo Xiaoting Wang Junrui Wang Pan Li Zhigang Wang Haitao Ran Zhiyi Zhou Xiaoyuan Chen Jingjing Zhang Jianli Ren Department of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imaging the Second Affiliated Hospital of Chongqing Medical UniversityChongqingP.R.China Department of Intensive Care Unit the Second Affiliated Hospital of Chongqing Medical UniversityChongqingP.R.China Department of Radiology the Second Affiliated Hospital of Chongqing Medical UniversityChongqingP.R.China Department of General Practice Chongqing General HospitalChongqingP.R.China Department of Diagnostic Radiology Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Nanomedicine Translational Research Program NUS Center for NanomedicineYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore

The blockade of cytoprotective autophagy has been demonstrated to effectively enhance the efﬁcacy of sonodynamic therapy(SDT).However,the limited recogni-tion of antiautophagy agents for autophagosomes impedes the clinical application of autophagy *** efﬁciently deliver hydroxychloroquine(HCQ),an autophagy inhibitor,to autophagosomes,we utilized a strategy based on in situ click chemistry between sulfhydryl(-SH)and maleimide(Mal)groups to trigger autophagosomes tracking and suppress tumor growth synergistically.A cascade nanoreactor was synthesized by encapsulating Mal-modiﬁed HCQ(MHCQ)into a manganese porphyrin-based metal-organic framework with sonosensitizer proper-ties,followed by poly(ethylene glycol)ylated liposomal membrane *** ultrasound irradiation,SDT-induced apoptotic cells released damaged proteins with free-SH groups,which MHCQ rapidly captured in situ via a Mal-thiol click *** autophagosomes actively wrapped damaged proteins for detoxiﬁ-cation,they simultaneously internalized HCQ anchored on *** this scenario,antiautophagy drugs could actively track intracellular autophagosomes instead of undergoing passive diffusion in the *** interaction between HCQ and autophagic vesicles was greatly enhanced,which strengthened the blocking efﬁ-ciency of autophagy and resulted in complete cell ***,this study with smart design provides a promising strategy for improving intracellular targeted delivery to autophagosomes,thereby enhancing antitumor therapy.

关键词： autophagosomes tracking autophagy blockade click reaction sonodynamic therapy synergy

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