Clearing intratumoral bacteria to augment tumor-therapeutic response by engineering antimicrobial dendritic mesoporous silica nanomedicine

Abstract

As an important component of the tumor microenvironment, the intratumoral bacteria can significantly reduce the chemotherapeutic response, in which Fusobacterium nucleatum has been established as the representative intratumoral bacteria in colorectal cancer, promoting chemotherapy resistance by activating autophagy pathways. Herein, the concept of antibacterial-augmented antitumor nanomedicine for pathogen-related cancer therapy was elaborated by designing antibacterial-antineoplastic nanoagents that modulate intratumoral bacteria to augment anticancer efficiency. A generic coordination-redox strategy was used for homogeneous in situ growth of antibacterial ultrasmall silver nanoparticles into the dendritic mesoporous silica nanoparticles, which were further loaded with chemotherapeutic drugs. The antibacterial-antineoplastic agents exhibited excellent antitumor efficacy by scavenging Fusobacterium nucleatum to modulate autophagy, thereby overcoming chemoresistance to heighten the therapeutic effect. This work proposes a conceptual framework of antibacterial-augmented antitumor nanomedicine for refined cancer-therapeutic efficacy by modulating intratumoral bacteria to enhance therapeutic responses of chemotherapy, opening new horizons on nanomedicine design for more effective tumor therapy.