The colorectal cancer-specific microbiome regulation and immune response activation via an artificial biomimetic nanovaccine

Abstract

The tumor microbiome has been reported to be composed of tumor-type-specific intracellular bacteria and is closely related to tumor progression and the response to anticancer therapies. Although antitumor treatments focusing on the abnormal tumor microenvironment (TME), such as anti-bacterial or TME regulatory approaches, have been shown to significantly improve antitumor efficacy, strategies that can interfere with the microbial environment to inhibit tumor growth and activate immune response are rare. Here, we have constructed an artificially modified biomimetic nanovaccine PMO for the first time using an inactivated anaerobic bacterium P. anaerobius, a colorectal cancer (CRC)-specific bacterium carrying therapeutical agents to regulate the microbial environment. The PMO could sneak into tumors due to its natural affinity to CRC, which has a particularly rich and diverse microbiome that results in therapy resistance. The PMO could not only achieve significant tumor growth suppression by precisely delivering therapeutical MnO2 and OXA to CRC tissues but also effectively prevent tumor recurrence by the cascade reaction of activating the tumor immune responses after reshaping the microbial environment. This nanovaccine has provided the tremendous clinical potential for designing new treatment strategies for drug-resistant tumors from the perspective of microbial environmental regulation and improving the prognosis of patients.