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 (AuNNP@MnO2 Ve@BSA). The MnO2 shell was etched when AuNNP@MnO2 Ve@BSA vesicle was exposed to GSH, the gap between intra-vesicular AuNNP@MnO2 NPs was reduced. This significantly enhanced the plasmonic coupling effect between AuNNP@MnO2 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 AuNNP@MnO2 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. [Display omitted] •GSH-responsive localized aggregation vesicles were designed to enhance X-ray sensitization accompanied by a NIR-II PA signal.•The NIR-II PA imaging dynamic processes of the vesicles are inducible at a record tissue depth is 5 cm.•The error of deep tumor volume measured by NIR-II PA imaging of the vesicles was less than 10%.•The vesicles enabled the maximum enhancement of radiosensitization, and maximum reduction of side effects.