Biodegradable Poly(amino acid)-Bismuth Nanotheranostic Agents for CT/MR Imaging and Photothermal-Chemodynamic...

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.