NIR-II Multimodal Phototheranostics Synergized with Antigen-Specific Vaccines for Boosted Cancer Photoimmunotherapy.

Photoimmunotherapy offers precise tumor ablation and systemic immunity through immunogenic cell death and cytotoxic T-cell activation. Among immunotherapies, antigen-specific vaccines targeting well-defined tumor antigens are particularly promising for personalized cancer treatment due to their durable immune surveillance and precise activation with minimal off-target effects. However, their integration with phototherapy remains almost unexplored. Herein, we report a synergistic strategy combining an antigen-specific vaccine with phototherapy. Specifically, motivated by the advantageous merits of multimodal phototheranostics, a multimodal phototheranostic agent (TBBSD) was rationally designed as the phototherapy module, while the hepatocellular carcinoma (HCC)-specific antigen glypican-3 (GPC3) protein and adjuvant cyclic diadenylate (c-di-AMP) were employed as the antigen-specific vaccine. By means of the complementary advantages, this photoimmunotherapeutic strategy achieves efficient ablation of primary tumors, simultaneously induces a robust systemic immune response, and fosters long-term immunological memory, which synergistically prevents tumor recurrence and suppresses the growth of both distant and pulmonary metastatic lesions. Collectively, these results underscore the therapeutic reliability and translational potential of this efficacious photoimmunotherapy strategy for precision cancer treatment.