Platinum micromotors for mucosal penetration and colorectal cancer therapy

Qiang Yang; Ya Ma; Menghang Zu; Xinghong Cai; Qiang Gao; Yingui Cao; Ga Liu; Yajun Wang; Bo Xiao; Jun Zhang

doi:10.1016/j.ijpharm.2025.125201

Platinum micromotors for mucosal penetration and colorectal cancer therapy

Int J Pharm. 2025 Jan 10:670:125201. doi: 10.1016/j.ijpharm.2025.125201. Online ahead of print.

Authors

Qiang Yang¹, Ya Ma², Menghang Zu³, Xinghong Cai², Qiang Gao², Yingui Cao², Ga Liu², Yajun Wang⁴, Bo Xiao⁵, Jun Zhang⁶

Affiliations

¹ Clinical Center for Tumor Therapy, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China; State Key Laboratory of Resource Insects, College of Sericulture, Textile, and Biomass Sciences, Southwest University, Chongqing 400715, China.
² State Key Laboratory of Resource Insects, College of Sericulture, Textile, and Biomass Sciences, Southwest University, Chongqing 400715, China.
³ State Key Laboratory of Resource Insects, College of Sericulture, Textile, and Biomass Sciences, Southwest University, Chongqing 400715, China; Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China.
⁴ Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China. Electronic address: yajunw24@uestc.edu.cn.
⁵ State Key Laboratory of Resource Insects, College of Sericulture, Textile, and Biomass Sciences, Southwest University, Chongqing 400715, China; Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China. Electronic address: bxiao@swu.edu.cn.
⁶ Clinical Center for Tumor Therapy, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. Electronic address: amend@cqmu.edu.cn.

PMID: 39800004
DOI: 10.1016/j.ijpharm.2025.125201

Abstract

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.

Keywords: Colonic mucosal penetration; Colorectal cancer; H(2)O(2)-driven; PLGA-Pt micromotor.