Platinum micromotors for mucosal penetration and colorectal cancer therapy

The therapeutic outcomes of medications were restricted by the colonic mucosal barrier during the treatment of colorectal cancer (CRC). Micro/nanomotors can overcome the mucus barriers to reach deep colorectal tumors. In this study, we constructed a novel microsized PLGA-Pt micromotor (MM) driven by hydrogen peroxide (H₂O₂) to enhance drug delivery to the CRC tissues and achieve effective antitumor therapy. The PLGA-Pt MMs actively traversed the colonic mucosal barrier with the assist of gas propulsion, while continuously releasing Pt²⁺ ions within the tumor microenvironment. In vitro studies revealed that the PLGA-Pt MMs exhibited rapid movement in the presence of H₂O₂, achieving superior colonic mucosal penetration. It effectively delivered Pt²⁺ ions to the nuclei, forming DNA-Pt adducts that induced significant DNA damage and apoptosis of CRC cells. In vivo studies showed the PLGA-Pt MM significantly suppressed orthotopic tumor growth and activated antitumor immunity, enhancing the therapeutic effect against CRC. This study presents a micromotor capable of overcoming mucosal barriers for efficient treatment of orthotopic CRC.