A Biomimetic Sweeping Microrobot for Active Therapy of Ulcerative Colitis

Abstract Overproduction of pathogenic cell‐free DNA (cfDNA) and reactive oxygen species (ROS) plays crucial roles in the onset and perpetuation of ulcerative colitis (UC). Inspired by sweeping robots, a magnesium@polylactic acid‐glycolic acid copolymer@polyethylenimine (Mg@PLGA@PEI) microswimmer capable of cleaning off deleterious disease triggers along its path of progress is designed. Mg@PLGA@PEI is successfully synthesized by adopting a core‐shell structure with a small opening which allows for Mg‐water reaction. The distinctive motility performance resulting from sustained detachment of the produced hydrogen not only contributes to strengthened hydrogen diffusion concomitant with potentiated ROS neutralization, but also facilitates the contacting probability with microenvironmental cfDNA and thus enhances the DNA binding efficiency. By integrating these merits, the developed Mg@PLGA@PEI confers desirable curative efficacy in a classical DSS‐induced acute colitis mouse model. Enema administration of Mg@PLGA@PEI microswimmers substantially alleviates the manifestations related to UC, as evidenced by the body weight recovery, colon length retention, colon tissue protection, and attenuated intestinal inflammation, which is attributed to the active scavenging of cfDNA and ROS. This work provides a paradigm for a drug‐free strategy competent in spontaneously eliminating causative triggers with minimal side effects, which presents a promising alternative for the active therapy of UC or other cfDNA‐ and ROS‐related diseases in the clinic.