Turning harm into benefit: Harnessing intratumoral bacteria as immunopotentiators for cascade-enhanced therapy of bacteria-associated colorectal cancer

Immunotherapy has shown promise in colorectal cancer, yet many patients fail to achieve satisfactory responses due to the immunosuppressive tumor microenvironment promoted by intratumoral Fusobacterium nucleatum ( Fn ) colonization. Additionally, tumor hypoxia favors anaerobic bacterial growth while compromising oxygen-dependent therapies. Herein, a “turning harm into benefit” cascade strategy is developed to transform intratumoral bacteria from harmful factors into immunopotentiators through the ultrafacile intratumoral injection of potassium permanganate (KMnO₄). This KMnO₄-based cascade strategy not only utilizes its strong oxidative properties to achieve bactericidal and tumoricidal effects but also alleviates tumor hypoxia through in situ MnO₂ generation. Furthermore, it substantially enhances the subsequent cascade of Ce6-mediated sonodynamic therapy and anti-programmed death-ligand 1 (αPD-L1)-mediated immunotherapy for bacteria-associated colorectal cancer through multistep, orderly amplification effects. Besides, this in situ generation strategy achieves high raw material utilization and enables specific responsiveness to the tumor microenvironment. Compared to conventional nanomaterials, it also eliminates the need for complex external preparation and purification processes and overcomes the limitation of low tumor accumulation efficiency. Overall, the KMnO₄-based cascade strategy enabled by minimalist in situ injection provides a novel and practical approach for the treatment of bacteria-associated tumors.