Biomineralized outer membrane vesicles for synergistic immuno-photodynamic therapy of oral squamous cell carcinoma.

Immunotherapy against oral squamous cell carcinoma (OSCC) currently exhibits a clinical response rate significantly lower than anticipated, underscoring the need for more effective therapeutic strategies. Outer membrane vesicles (OMVs) represent promising natural immune modulators; however, their systemic application is limited by risks such as cytokine storms and inadequate tumor accumulation. To overcome these challenges, this study developed biomineralized OMVs coated with calcium phosphate (CaP) and subsequently loaded with the photosensitizer chlorin e6 (Ce6) on the surface, termed OMVs@CaP-Ce6 (OCC). The resulting OCC demonstrates enhanced tumor accumulation and responsiveness to acidic conditions, including the tumor microenvironment (TME). Under acidic pH conditions, the CaP shell disintegrates, releasing both OMVs and Ce6 to enable synergistic immunotherapy and photodynamic therapy (PDT). PDT promotes cancer cell apoptosis, while OMVs activate antitumor immunity by modulating immune responses. Studies demonstrate that OCC, as a highly biocompatible and synergistic platform, effectively suppresses tumor growth under laser irradiation by eliminating cancer cells and reversing the immunosuppressive TME to enhance antitumor immunity. This spatiotemporal and biomineralized OCC system maximizes the immunotherapeutic potential of OMVs, overcomes the limitations of conventional monotherapies, and offers a promising alternative strategy for the effective treatment of OSCC.