Natural-Inspired Engineered Microalgae With Selenium Enrichment Enabled Potent Anti-Tumor Immunity

Immunotherapy has shed light on clinical oncology for several decades. However, it still suffers from heterogeneous therapeutic outcomes and potential immune-related adverse events (irAEs). Inspired by a natural phenomenon that microalgae can absorb and accumulate selenium (Se), a well-known healthcare element, we engineered a Se-enriched cyanobacterium Synechococcus Sp (Se-Ssp) for advanced immunotherapy. Simply by culturing in the presence of Na₂SeO₃, Se nanoparticles could be bio-fabricated within Synechococcus Sp, underscoring a facile preparation process with promising translational potential. With satisfactory biocompatibility and internalization efficiency, Se-Ssp boosted dendritic cell maturation and antigen presentation via both the Toll-like receptor and the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathways, likely attributed to the Se-enhanced influx of calcium. In vivo studies demonstrated that Se-Ssp elicited potent innate immunity and maintained long-term adaptive immunity, effectively inhibiting tumor growth with sustained protection against recurrence. In addition, Se-Ssp was validated to sensitize the reaction of both primary and distant tumors to immune checkpoint and indoleamine 2,3-dioxygenase inhibitors; it also restrained the progression of orthotopic bladder carcinoma via intravesical instillation as well. Briefly, this study developed an anti-cancer immune application of engineered Se-Ssp, offering a promising alternative with significant therapeutic potential that might benefit patients with cancer.