Albumin-templated biomineralizing growth of composite nanoparticles as smart nano-theranostics for enhanced radiotherapy of tumors

Abstract

Hypoxia and a dense extracellular matrix within the tumor microenvironment can often lead to the resistance of tumors to radiotherapy. Herein, we use bovine serum albumin (BSA) as a template to induce the growth of both gold (Au) nanoclusters and manganese dioxide (MnO₂) via biomineralization. In the obtained BSA-Au-MnO₂ composite nanoparticles, Au nanoclusters embedded within BSA not only show strong red fluorescence to facilitate imaging, but also act as a radio-sensitizer by absorbing and depositing X-ray energy within tumors to enhance radiotherapy. Meanwhile, the MnO₂ core, which enables the formation of composite nanoparticles by connecting multiple albumins together, is able to modulate the tumor hypoxia by triggering the decomposition of tumor endogenous H₂O₂ into oxygen, so as to reverse the hypoxia-associated radiation resistance of tumors. Notably, such BSA-Au-MnO₂ composite nanoparticles with larger sizes show prolonged blood circulation and increased tumor accumulation compared to BSA-Au complexes, and would dissociate back into individual BSA-Au complexes once inside the tumor with reduced pH to allow deep interstitial diffusion. As a result, highly effective radiotherapy of tumors is realized with these nanoparticles in a mouse tumor model. Our work thus presents a convenient biomineralization approach to fabricate intelligent multifunctional nanoparticles composed of biocompatible/biodegradable components for enhanced cancer therapy.