Bacterium-Inspired Nanoagents Armed With On-Switch Of Immune Recruitment And Immune Activation

Bacterium-based immunotherapy holds promise for tumor eradication, yet its application is hindered by significant safety concerns. Inspired bacteria, an immunity-switch nanotherapeutic termed FMaP, for precise immunity control is developed. This nanotherapeutic remains immunologically inert (immunity-off) during its circulation period but elicits immune-associated activity (immunity-on) upon reaching tumors. The FMaP nanoconstruction is composed of 1) a magnetic nanoparticle (MNP) nanocore, 2) a bacteria-derived chemotactic peptide conjugated onto MNP, and 3) a bacterial capsule-like polyethylene glycol (PEG) corona coupled via a tumor-labile linkage. The PEG corona acts as the off-on switch to enable FMaP immune-off under normal conditions. Upon magnetotactic entry into acid tumors, the PEG corona can escape to expose the chemotactic peptide, functioning as the on-switch to initiate immunoregulation of intratumoral immune cells and site-specific recruitment of circulating immune cells. Compared with the performance of bacteria, FMaP shares most of their immune features but avoids their toxicity. FMaP demonstrates high immunotherapeutic potency either alone or in combination with chemotherapy and immune checkpoint blockade therapy toward colon carcinoma and melanoma tumor models, showing versatile adaptability for treating multiple tumor types. This study offers a paradigm of how to rationally design materials by seeking advantages from micro-organisms.