In situ oxidation-responsive nanovaccine coordinates photosensitizer and STING agonist for cancer photo-immunotherapy

Cancer vaccine has emerged as a promising therapeutic paradigm for cancer therapy. However, the lack of tumor-associated antigens and abundant immunosuppressive factors seriously diminish the efficacy of immunotherapy, resulting in poor clinical benefits. In this report, we engineered a coordinated immunostimulatory nanoplatform, termed MP@PPS NPs, by physically combining reactive oxygen species (ROS)-responsive poly (propylene sulfide) nanoparticles loaded with the photosensitizer pyropheophorbide a (PPa) and stimulator of interferon genes (STING) agonist (MSA-2), to function as an in situ cancer vaccine to amplify immunotherapeutic outcomes. Excellent stability of MP@PPS NPs endowed prolonged drug circulation time and improved tumor accumulation, while their small size boosted deeper drug penetration within tumors. Crucially, upon laser irradiation, the MP@PPS NPs could generate abundant ROS, which induced tumor ablation, triggered immunogenic cell death to initiate an adaptive antitumor immune response and facilitated the local release of MSA-2, thereby promoting innate antitumor immunity through the cGAS-STING pathway. MP@PPS NPs markedly suppressed both primary and distant tumor progression, promoted dendritic cell maturation and increased cytotoxic T lymphocyte infiltration, elicited robust antitumor immunity. Meanwhile, MP@PPS NPs treatment impeded the lung metastatic in conjunction with anti-PD-L1 treatment. This work holds significant promise for the synergistic photodynamic immunotherapy, and offers a crucial inspiration for addressing the problems of insufficient antitumor immunity and ineffective cancer treatments.