Spatiotemporally confined assembly of radiosensitizers for synergistic radio-chemodynamic therapy on deep tumor of rabbit

The controllable assembly of nanoparticles significantly improves their biological effects in vivo. However, it is difficult to realize the assembly regulation of nanomaterials under complex physiological conditions. Herein, endogenous glutathione (GSH)-triggered vesicles with spatiotemporally confined aggregation of gold nanogapped nanoparticles (AuNNPs) within vesicles were developed. These vesicles had excellent photoacoustic (PA) imaging capability in the near-infrared second window (NIR-II) for precise localization of deep tumors, measuring tumor volume, and making deep tumors more sensitive to radiotherapy and chemodynamic therapy (CDT). The vesicles were prepared via self-assembly of MnO2-coated AuNNPs that were functionalized by phosphate-polystyrene and bovine serum albumin ([email protected]2 [email protected]). The MnO2 shell was etched when [email protected]2 [email protected] vesicle was exposed to GSH, the gap between intra-vesicular [email protected]2 NPs was reduced. This significantly enhanced the plasmonic coupling effect between [email protected]2 NPs, giving it excellent NIR-II PA imaging capability, and thus can be used to delineate the boundary and volume of deep-seated tumors. Meanwhile, the Mn2+-mediated CDT released after the etching of the MnO2 shell interacted with GSH-responsive [email protected]2 [email protected] and significantly inhibited tumor growth due to enhanced radiosensitization effect. This unique strategy provides new perspectives and methods for designing and applying biomedical nanomaterials.