Nanozyme-Coated Bacteria Hitchhike on CD11b⁺ Immune Cells to Boost Tumor Radioimmunotherapy

Bacterial-based delivery strategies have recently emerged as a unique research direction in the field of drug delivery. However, bacterial vectors are quickly phagocytosed by immune cells after entering the bloodstream. Taking advantage of this phenomenon, herein, this work seeks to harness the potential of immune cells to delivery micron-sized bacterial vectors, and find that inactivated bacterial can accumulate at tumor-site after intravenous injection through CD11b(+) cells hitchhiking. To this end, this work then designs a gold-platinum bimetallic nanozyme coated bacterial vector (Au-Pt@VNP20009, APV). Utilizing strong tumor inflammatory response induced by low dose X-rays, this work further heightens the ability of CD11b(+) immune cells to assist APV hitchhiking for tumor-targeted delivery, which can significantly relieve tumor hypoxia and immunosuppression, and inhibit tumor growth and metastasis. This work elucidates the potential mechanisms of bacterial vector targeted delivery, opening up new horizons for bacterial vector delivery strategies and clinical tumor radioimmunotherapy.