Chemically Programmed Living Catalytic Probiotics to Overcome Fungal Barriers in Antitumor Immunotherapy

Gut fungal dysbiosis is increasingly recognized as a critical regulator of tumor immunity and a barrier to effective antitumor immunotherapy. However, most current antifungal or microbiota-based strategies focus primarily on fungal elimination with limited ability to translate immune modulation into durable therapeutic benefit. Here, we developed a chemically programmed living catalytic probiotic platform, mGa@Lr-CaNC, by integrating inorganic functional modules with viable probiotics without genetic modification. Following oral administration of this living catalytic probiotic platform, fungal iron metabolism was selectively disrupted, resulting in normalization of gut mycobiome homeostasis and alleviation of systemic immunosuppression. Concurrently, the living catalytic probiotics exerted catalytic activity within the tumor microenvironment, enhancing cancer cell killing and eliciting robust antitumor immune responses. This coordinated chemical–biological process achieved pronounced antitumor efficacy in colon and pancreatic mouse models. Importantly, this non–genetically engineered living chemical–biological platform establishes a modular and flexible design framework for tackling complex therapeutic challenges, providing a conceptual blueprint for the development of organic–inorganic hybrid systems in biomedical applications.