Biohybrid Microrobot Enteric-Coated Microcapsule for Oral Treatment of Colorectal Cancer

The oral treatment of colorectal cancer is highly desirable due to its noninvasiveness and potential for localized drug action, yet it remains challenged by gastrointestinal barriers and limited intratumoral penetration. This study presents the first oral biohybrid microrobot system that integrates ultrasound-activated piezoelectric catalysis with bacterial therapy, achieving synergistic tumor targeting, reactive oxygen species generation, and immune activation. By leveraging Enterobacter aerogenes (EA) and BaTiO₃ nanoparticles, this strategy induces immunogenic tumor cell death and metabolic remodeling. It utilizes BaTiO₃ incorporated into EA (EA@BTO) microrobots, which are encapsulated in enteric microcapsules. These microcapsules, encapsulated in enteric microcapsules via photocurable 3D printing, protect during digestion, target tumors, penetrate mucus, and release gases. They thrive in anaerobic, acidic environments, enabling precise, responsive delivery within the intestinal tract. Once the microrobots reach the tumor, the BaTiO₃ nanoparticles catalyze reduction and oxidation reactions upon ultrasound irradiation, leading to the induction of immunogenic tumor cell death. Notably, the consumption of lactic acid by BaTiO₃ and EA alleviates the immunosuppressive microenvironment within the tumor. This promotes the maturation of dendritic cells and the polarization of macrophages toward the M1 phenotype, thereby reducing the proportion of regulatory T cells and enhancing the population of effector T cells.