Sprayable Lactococcus lactis-Nanocatalyst Gel for Postsurgical Immunomodulation in Preclinical Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most prevalent and aggressive head and neck cancers. Emerging evidence shows that distinct microbiomes coexist with tumor and immune cells in the tumor microenvironment (TME), shaping tumor progression and antitumor immunity. Harnessing probiotic-based immune modulation therefore represents a promising strategy to improve postoperative outcomes. Here, we develop a dual-channel sprayable Lactococcus lactis probiotic-nanocatalyst gel (L. lactis@Co4N/C@Gel) to potentiate postoperative immune reconstruction in OSCC. L. lactis can activate antitumor responses through Toll-like and NOD-like receptor pathways. However, its therapeutic benefit is constrained by lactate overproduction, which promotes tumor aggressiveness, immunosuppression, and therapy resistance. The incorporated Co4N/C nanoparticles efficiently scavenge L. lactis-derived lactate, thereby amplifying downstream immune activation. Benefiting from the thixotropic properties of calcium alginate, a sodium alginate solution containing L. lactis and CaCl2 solution containing Co4N/C nanoparticles can be cosprayed to achieve uniform wound coverage and rapid in situ gelation. In an orthotopic OSCC mouse model, L.lactis@Co4N/C@Gel effectively reconstructs postoperative antitumor immunity and markedly suppresses tumor recurrence. These findings highlight a microbiome-nanocatalyst synergistic strategy for improving postoperative immunotherapy in OSCC.