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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.
Li, Jun; Zhang, Qiang; Yang, Hao; Lu, Wenli; Fu, Yulong; Xiong, Yingcai; Wang, Xuan; Lu, Tianming; Xin, Yanlin; Xie, Zejuan; Chen, Weichao; Wang, Guoqiang; Guo, Yuanyuan; Qi, Ruogu.
Afiliación
  • Li J; School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Zhang Q; School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Yang H; School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Lu W; School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Fu Y; Key Laboratory of Mesoscopic Chemistry of Ministry of Education, Institute of Theoretical and Computational Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
  • Xiong Y; School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Wang X; School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Lu T; School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Xin Y; School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Xie Z; School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Chen W; Laboratory for Manufacturing Low Carbon and Functionalized Textiles, College of Textiles & Clothing, Qingdao University, Qingdao 266071, China.
  • Wang G; Key Laboratory of Mesoscopic Chemistry of Ministry of Education, Institute of Theoretical and Computational Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
  • Guo Y; School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Qi R; School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Acta Pharm Sin B ; 14(7): 3251-3265, 2024 Jul.
Article en En | MEDLINE | ID: mdl-39027238
ABSTRACT
Selective activation of Pt(IV) prodrugs within tumors has emerged as a promising strategy in tumor treatment. Although 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 toxicity. In this study, a sequential dual-locked Pt(IV) nano-prodrug that can be activated by both the acidic tumor microenvironment and light was developed. The 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 prodrug. Under 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 tumor-associated macrophages (TAM), thereby enhancing tumor inhibition. The 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Acta Pharm Sin B Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Acta Pharm Sin B Año: 2024 Tipo del documento: Article País de afiliación: China