Light-Mediated In Situ Synchronous Capture of Antigens and Nucleic Acids as Nanovaccines to Boost Tumor Radioimmunotherapy

Radiotherapy-induced immunogenic cancer cell death to generate vaccine effects is an effective approach to enhancing the efficacy of tumor therapy. However, it is often constrained by insufficient uptake of released tumor antigens and damage-associated molecular patterns (DAMPs) by dendritic cells (DCs). To address this issue, a light-mediated strategy for synchronous capture of antigens and nucleic acid adjuvants is reported to in situ generate vaccines for enhanced tumor radioimmunotherapy. A type of light-responsive nanoparticle fAuNPs-Ce6 is rationally designed and fabricated by modifying 3-(2-furyl) propanoic acids and photosensitizer Chlorin e6 (Ce6) on the surface of gold nanoparticles. Under the catalysis of 1 O 2 generated from Ce6 upon a 660 nm laser irradiation, fAuNPs-Ce6 nanoparticles can capture the tumor-derived protein antigens and nucleic acid fragments simultaneously through the furan-mediated covalent reactions with amino group or nucleobase, which significantly prolongs the retention time of antigens and adjuvants in the tumor microenvironment, promoting robust DC maturation without exogenous adjuvants and eliciting potent systemic antitumor immunity. More notably, these nanovaccines in combination with PD-L1 blockade can remarkably enhance the radiotherapeutic efficacy, achieving significant suppression of both primary and distant tumor growth. Therefore, this light-mediated in situ vaccination may offer a promising strategy for the precise treatment of malignant tumors.