Biodegradable Poly(amino acid)–Bismuth Nanotheranostic Agents for CT/MR Imaging and Photothermal–Chemodynamic Synergistic Therapy

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