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 MnO 2 -coated AuNNPs that were functionalized by phosphate-polystyrene and bovine serum albumin (AuNNP@MnO 2 Ve@BSA). The MnO 2 shell was etched when AuNNP@MnO 2 Ve@BSA vesicle was exposed to GSH, the gap between intra-vesicular AuNNP@MnO 2 NPs was reduced. This significantly enhanced the plasmonic coupling effect between AuNNP@MnO 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 Mn 2+ -mediated CDT released after the etching of the MnO 2 shell interacted with GSH-responsive AuNNP@MnO 2 Ve@BSA and significantly inhibited tumor growth due to enhanced radiosensitization effect. This unique strategy provides new perspectives and methods for designing and applying biomedical nanomaterials.