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

Abstract

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.