Antibiotic-based micelles with bone-targeting and pH-responsive properties for infectious osteomyelitis treatment

Xinyu Lu; Xiaohui Wan; Jiali Lian; Jiaoying Peng; Pei Jing; Qiao Guo; Yulong Liao; Yuchen Jiang; Chengli Yang; Lunqiang Jin; Shaorui Shi; Yongchao Yao; Wenchuang Walter Hu; Jianbin Luo

doi:10.1016/j.jcis.2025.01.136

Antibiotic-based micelles with bone-targeting and pH-responsive properties for infectious osteomyelitis treatment

J Colloid Interface Sci. 2025 Jan 17:685:648-660. doi: 10.1016/j.jcis.2025.01.136. Online ahead of print.

Authors

Xinyu Lu¹, Xiaohui Wan², Jiali Lian², Jiaoying Peng³, Pei Jing⁴, Qiao Guo², Yulong Liao³, Yuchen Jiang², Chengli Yang³, Lunqiang Jin³, Shaorui Shi⁵, Yongchao Yao⁶, Wenchuang Walter Hu⁷, Jianbin Luo⁸

Affiliations

¹ College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041 China; Precision Medicine Translational Research Center, West China Hospital, Sichuan University, Chengdu 610041 China.
² College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041 China.
³ Precision Medicine Translational Research Center, West China Hospital, Sichuan University, Chengdu 610041 China.
⁴ Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, China.
⁵ Department of Laboratory Medicine, The Second People's Hospital of Yibin, West China Hospital, Yibin Hospital Sichuan University, Yibin 644000 China. Electronic address: [email protected].
⁶ Precision Medicine Translational Research Center, West China Hospital, Sichuan University, Chengdu 610041 China. Electronic address: [email protected].
⁷ Precision Medicine Translational Research Center, West China Hospital, Sichuan University, Chengdu 610041 China. Electronic address: [email protected].
⁸ College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041 China. Electronic address: [email protected].

PMID: 39862844
DOI: 10.1016/j.jcis.2025.01.136

Abstract

We developed antibiotic-based micelles with bone-targeting and charge-switchable properties (P-CASMs) for treating infectious osteomyelitis. The amphiphilic molecules are formed by combining ciprofloxacin (CIP) with ligand 1 through a mild salifying reaction, and spontaneously self-assemble into antibiotic-based micelles (ASMs) in aqueous solution. Acrylate groups on ligand 1 enable cross-linking of ASMs with pentaerythritol tetra(mercaptopropionate) via a click reaction, forming pH-sensitive cross-linked micelles (CASMs). The incorporation of vinylphosphonates imparts bone-targeting and charge-switchable properties of CASMs, creating P-CASMs. These P-CASMs exhibit good biocompatibility at physiological pH and strong adhesion to bone infection sites (pH 5.5) due to electrostatic interactions. They can effectively penetrate bacterial biofilms and release antibiotics in response to the local microenvironment, thereby eradicating bacteria. Compared to previous systems, the P-CASMs show higher drug loading (∼23 %), improved stability, and better biosafety. This innovative system holds substantial potential for clinical applications in the treatment of osteomyelitis.

Keywords: Antibiotic-based micelles; Bacterial osteomyelitis; Bone targeting; Surface charge; pH responsive.