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Sequential dual-locking strategy using photoactivated Pt(Ⅳ)-based metallo-nano prodrug for enhanced chemotherapy and photodynamic efficacy by triggering ferroptosis and macrophage polarization

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3251-3265页

作者： Jun Li Qiang Zhang Hao Yang Wenli Lu Yulong Fu Yingcai Xiong Xuan Wang Tianming Lu Yanlin Xin Zejuan Xie Weichao Chen Guoqiang Wang Yuanyuan Guo Ruogu Qi School of Medicine Nanjing University of Chinese MedicineNanjing 210023China Key Laboratory of Mesoscopic Chemistry of Ministry of Education Institute of Theoretical and Computational ChemistrySchool of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China Laboratory for Manufacturing Low Carbon and Functionalized Textiles College of Textiles&ClothingQingdao UniversityQingdao 266071China

Selective activation of Pt(Ⅳ)prodrugs within tumors has emerged as a promising strategy in tumor *** progress has been made with photo-and ultrasound-activated Pt(Ⅳ)prodrugs,concerns remain over the non-specific activation of photosensitizers(PS)and the potential for phototoxicity and chemical *** this study,a sequential dual-locked Pt(Ⅳ)nano-prodrug that can be activated by both the acidic tumor microenvironment and light was *** Pt(Ⅳ)prodrug was prepared by conjugating PS-locked Pt(Ⅳ)to a polymeric core,which was then chelated with metallo iron to lock its photoactivity and form a metallo-nano *** acidic tumor microenvironment conditions,the metallo-nano prodrug undergoes dissociation of iron,triggering a reduction process in oxaliplatin under light irradiation,resulting in the activation of both chemotherapy and photodynamic therapy(PDT).Additionally,the prodrug could induce metallo-triggered ferroptosis and polarization of tumorassociated macrophages(TAM),thereby enhancing tumor *** dual-lock strategy employed in a nanoparticle delivery system represents an expansion in the application of platinum-based anticancer drugs,making it a promising new direction in cancer treatment.

关键词： dual-locking Pt(Ⅳ)reduction Chemotherapy Photodynamic therapy Ferroptosis Macrophage polarization Medicinal inorganic chemistry Metals in medicine

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