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

• Main Authors: Jun Li (Author), Qiang Zhang (Author), Hao Yang (Author), Wenli Lu (Author), Yulong Fu (Author), Yingcai Xiong (Author), Xuan Wang (Author), Tianming Lu (Author), Yanlin Xin (Author), Zejuan Xie (Author), Weichao Chen (Author), Guoqiang Wang (Author), Yuanyuan Guo (Author), Ruogu Qi (Author)
• Format: Book
• Published: Elsevier, 2024-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

2211-3835
10.1016/j.apsb.2024.02.024