Unified inactivation-mineralization: An engineered bacterial platform for synergistic radio-immunotherapy

Radiotherapy (RT) can induce immunogenic cell death (ICD) and stimulate antitumor immunity, but its efficacy is hindered by the immunosuppressive tumor microenvironment (TME). Herein, we develop an inactivated Pseudomonas aeruginosa (PAO1) vehicle by repurposing potassium permanganate (KMnO₄), a classic disinfectant, for the facile one-pot biomineralization and inactivation. This construct, PP-Mn-PAO1, serves as an integrated platform for concurrent radiosensitization and immune activation. The manganese oxide coating consumes glutathione (GSH) and amplifies radiation-induced reactive oxygen species (ROS), thereby enhancing ICD and dendritic cell maturation under low-dose irradiation. Moreover, the acidic tumor microenvironment triggers the release of Mn²⁺ along with bacterial components, which could activate the cGAS-STING pathway and promote the downstream antitumor immune responses. In the B16-OVA melanoma mouse model, PP-Mn-PAO1 combined with low-dose X-ray (2 Gy) achieves 66.7% primary tumor eradication and suppresses distal tumor growth. Additionally, the one-pot biomineralization enables rapid bacterial inactivation and efficient manganese oxide loading via a simplified procedure. This strategic integration of radio-enhancement and immune activation provides a scalable solution to boost radiotherapy and overcome immunosuppressive barriers.