Biodegradable Poly(amino\nacid)–Bismuth Nanotheranostic\nAgents for CT/MR Imaging and Photothermal–Chemodynamic Synergistic\nTherapy

Abstract

Clearly delineating the tumor foci based on multimodal\nimaging\ntechniques and precisely guiding the minimally invasive therapy are\npivotal to completely remove tumors, especially for early micro-tumor\nlesions. Nevertheless, single-mode imaging techniques are difficult\nto accurately visualize the tumor region, and the mono-therapeutic\nstrategy is hardly a complete removal of the tumor. In this study,\nwe prepare a biodegradable amphiphilic polymer containing poly(aspartic\nacid). It is further self-assembled with Bi³⁺ and ultrasmall\nFe₃O₄ to form a multifunctional nanocomplex\n(Bi/Fe₃O₄@P3), which served as a CT/MRI dual-imaging\ncontrast agent and enhanced the photothermal/chemodynamic synergistic\ntherapy. In addition, to enhance the photothermal efficiency, the\nthermal stress also elevated the level of intracellular H₂O₂, which would facilitate the Fenton reaction between\nBi³⁺/Fe²⁺ and H₂O₂ and\nimprove the chemodynamic therapy (CDT) efficacy. Particularly, Bi/Fe₃O₄@P3 would concurrently deplete the abundant intracellular\nGSH through the coordination of Bi³⁺ with GSH to further\npotentiate the PTT/CDT synergistic tumoricidal efficacy. Therefore,\nour study was expected to provide a promising theranostic nano-agent\nand potential comprehensive therapeutic strategy for microtumors.