Probiotic-motor armed with multifunctional artificial-enzymes augmented immunotherapy through evoking tumor...

Immunotherapy for melanoma is often limited by the low immunogenicity of tumors and an immunosuppressive tumor microenvironment (TME). Although immunogenic cell death (ICD) can remodel TME into an immunologically active one, insufficient ICD induction remains a major driver of therapeutic resistance. By coordinating apoptosis, necroptosis, and pyroptosis, PANoptosis markedly amplifies antigen presentation and cytokine release, thus constituting a highly inflammatory and potent form of ICD. Reactive oxygen species (ROS) act as an upstream signaling hub linking PANoptosis and ICD, yet ROS-driven therapeutic approaches are restricted by robust antioxidant defense, instability, and off-target toxicity. Here, anaerobic probiotics (Bac) selectively colonize hypoxic tumors and metabolically reprogram the acidic microenvironment to weaken antioxidant capacity, thereby sustaining ROS catalysis. Coupled with multifunctional artificial enzymes (OsCo), Bac enables tumor-targeted nanozyme delivery while functioning as a biological motor to amplify ROS generation, robustly inducing PANoptosis and ICD. This nanozyme-armed probiotic system (Bac@OsCo) establishes a self-reinforcing antitumor immune loop, remodels the TME, and offers a precise immunotherapeutic strategy for melanoma.