Photoactivatable nanoengineered microalgae (PCC@AuNP) generates hydrogen to induce immunogenic cell death while simultaneously remodeling the immunosuppressive tumor microenvironment through oxygen production and lactic acid depletion. This cascade-activated approach effectively eradicates primary tumors and elicits systemic antitumor immunity against distant metastatic lesions without observable toxicity, representing a promising precision cancer immunotherapy strategy.
Plain-Language Summary
Researchers developed a treatment using specially engineered microalgae (tiny algae cells) combined with gold nanoparticles that can be activated by light. When activated, this treatment produces hydrogen gas, which triggers cancer cells to die in a way that alerts the immune system. At the same time, it reduces the protective shield that tumors use to hide from the immune system. In mouse studies, this treatment eliminated primary tumors and prevented distant cancer spread without harming healthy tissue.
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.
