Polymyxin B-targeted liposomal photosensitizer cures MDR A. baumannii burn infections and accelerates wound healing via M1/M2 macrophage polarization

  • Zixin Cui
  • , Yiyang Li
  • , Yannan Qin
  • , Jianzhou Li
  • , Lei Shi
  • , Meijuan Wan
  • , Min Hu
  • , Yunru Chen
  • , Yanhong Ji
  • , Yuzhu Hou
  • , Chengcheng Liu
  • , Feng Ye

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Multidrug-resistant (MDR) Acinetobacter baumannii infections pose a significant challenge in burn wound management, necessitating the development of innovative therapeutic strategies. In this work, we introduced a novel polymyxin B (PMB)-targeted liposomal photosensitizer, HMME@Lipo-PMB, for precise and potent antimicrobial photodynamic therapy (aPDT) against burn infections induced by MDR A. baumanni. HMME@Lipo-PMB-mediated aPDT exhibited enhanced antibacterial efficacy by specifically targeting and disrupting bacterial cell membranes, and generating increased intracellular ROS. Remarkably, even at low concentrations, this targeted approach significantly reduced bacterial viability in vitro and completely eradicated burn infections induced by MDR A. baumannii in vivo. Additionally, HMME@Lipo-PMB-mediated aPDT facilitated burn infection wound healing by modulating M1/M2 macrophage polarization. It also effectively promoted acute inflammation in the early stage, while attenuated chronic inflammation in the later stage of wound healing. This dynamic modulation promoted the formation of granulation tissue, angiogenesis, and collagen regeneration. These findings demonstrate the tremendous potential of HMME@Lipo-PMB-mediated aPDT as a promising alternative for the treatment of burn infections caused by MDR A. baumannii.

Original languageEnglish
Pages (from-to)297-311
Number of pages15
JournalJournal of Controlled Release
Volume366
DOIs
StatePublished - Feb 2024

Keywords

  • Burn infections
  • Macrophage polarization
  • Multidrug-resistant Acinetobacter baumannii
  • Polymyxin B-targeted liposomal photosensitizer
  • Wound healing

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