Biomimetic nanodelivery system for precise elimination of tumor-infiltrating Escherichia coli and enhanced treatment of colorectal cancer

The development of colorectal cancer is closely related to the abnormal colonization of specific microorganisms in the tumor microenvironment. To address the challenges of exacerbated carcinogenesis and therapeutic resistance caused by Escherichia coli colonization in colorectal tumors, an innovative pH- and targeting-dual-responsive biomimetic nanodelivery system (CIP@EMV@CaCO 3 ) based on bacterial membrane biomimetic strategies was developed. This system employs E. coli -derived membrane vesicles (EMVs) as carriers to achieve dual functions of homologous targeting for antibacterial purposes and immune activation, overcoming the low delivery efficiency bottleneck of traditional antibiotics. The innovative incorporation of calcium carbonate (CaCO 3 ) enables both acidic environment-triggered lysosomal escape mediated by CO 2 microbubbles and immunotoxicity regulation, achieving a bacterial clearance rate of 99.14 %. Furthermore, the EMVs themselves were demonstrated to activate potent antitumor immune responses, inducing M1 macrophage polarization, promoting cytokine secretion, and enhancing T lymphocyte infiltration, resulting in a 98.02 % tumor suppression rate in E. coli -infected colorectal cancer models. This study provides a multifunctional precision therapeutic paradigm for regulating microbe-tumor interactions, demonstrating significant translational value in the synergistic field of targeted antibacterial and immune therapy.