Probiotic Engineering and Targeted Sonoimmuno‐Therapy Augmented by STING Agonist

Tumor targeting and effective immunomodulation are of critical significance during tumor treatment by sonodynamic therapy (SDT). Herein, the probiotic engineering of the clinically approved sonosensitizer (hematoporphyrin monomethyl ether (HMME)) is reported onto the probiotic bacterium Bifidobacteria Longum (BiL) for sonosensitive bifidobacterium construction (HMME@BiL cells). Based on the hypoxic tropism feature of the strain, effective tumor-targeted sonodynamic therapeutics can be achieved both in vitro and in vivo. To improve the immunological responses against tumor during sonodynamics, a recently-developed stimulator of interferon genes immune agonist SR717 has been employed to improve the anti-tumor immunity with prominent activities, eradicating both primary and metastatic tumors with high efficiency and satisfied biocompatibility. The present work provides a promising paradigm of microbiotic nanomedicine in a sophisticated sonoimmunotherapeutic strategy against malignant tumors.