Photoactivatable immunostimulatory nanoengineered microalgae for boosting cascade-activated antitumor immunity

Abstract

Limited tumor immunogenicity and the profoundly immunosuppressive tumor microenvironment (TME) pose major challenges to effective cancer immunotherapy. Herein, we present a photoactivatable immunostimulator based on nanoengineered microalgae (PCC@AuNP) to simultaneously enhance tumor immunogenicity and remodel the TME. Mechanistically, photocatalytically generated hydrogen induces robust immunogenic cell death by triggering severe endoplasmic reticulum stress and mitochondrial dysfunction. Concurrently, photosynthetic oxygen production and photocatalytic lactic acid depletion collaboratively alleviate immunosuppression within the TME, thereby enhancing cytotoxic T lymphocyte activity by reducing the infiltration of immunosuppressive cells and promoting the repolarization of tumor-associated macrophages from the M2 to the M1 phenotype. In vivo studies demonstrate that PCC@AuNP not only eradicates primary tumors but also elicits potent systemic antitumor immunity against distant lesions, without observable toxicity to healthy tissues. Collectively, this innovative PCC@AuNP platform offers a safe and effective therapeutic strategy, heralding a pioneering era of cascade-augmented gas-driven cancer immunotherapy with superior precision and biosafety.