Abstract
The clinical application of tumor vaccines is hindered by challenges such as time-consuming and costly production processes. In this context, in situ cancer vaccines represent a promising strategy by leveraging endogenous tumor antigens to elicit robust antitumor T cell responses. Herein, a photoactivatable tumor-targeting in situ nanovaccine, Lipo-D8-6, was constructed using cRGD-functionalized liposomes that co-encapsulated the photosensitizer chlorin e6 and a cleavable immunoadjuvant conjugate D8, allowing light-triggered synchronous activation of three therapeutic modules. Upon near-infrared light irradiation, Lipo-D8-6 generates reactive oxygen species that exert direct cytotoxicity on tumor cells and induce immunogenic cell death, while concurrently cleaving the responsive linker within D8 to achieve the controlled release of R848. In vivo biodistribution analysis confirmed the superior intratumoral accumulation of Lipo-D8-6, facilitating precise treatment. In a large-volume tumor model, the nanovaccine exhibited pronounced antitumor efficacy, accompanied by enhanced tumor infiltration of CD8(+) T cells. Overall, this work provides a simplified and effective approach for developing in situ nanovaccines that enable synergistic photodynamic immunotherapy with precise spatiotemporal control over immune activation.