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Surface charge switchable fluorinated small molecular micelles for enhanced photodynamic therapy for bacterial

Xinyu Lu1, Yuxuan He2, Jipeng Xiao3

  • 1College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, China; Precision Medicine Translational Research Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.

Journal of Colloid and Interface Science
|September 22, 2024
PubMed

Insights

Fluorinated micelles deliver oxygen to combat bacterial hypoxia, enhancing photodynamic therapy (PDT) effectiveness. This novel approach improves biofilm penetration and antibacterial activity for improved treatment outcomes.

Area of Science:

  • Biomedical Engineering
  • Photochemistry
  • Antimicrobial Research

Background:

  • Photodynamic therapy (PDT) utilizes photosensitizers (PS) and reactive oxygen species (ROS) to combat bacterial infections, including multi-drug resistant strains.
  • Hypoxic environments, common in infection sites and biofilms, significantly limit PDT efficacy by reducing ROS generation.
  • Developing strategies to overcome hypoxia is crucial for enhancing PDT's antimicrobial potential.

Purpose of the Study:

  • To develop and evaluate novel fluorinated small molecular micelles (PF-CBMs) as carriers for photosensitizers in PDT.
  • To investigate the role of perfluorocarbons in oxygen delivery and biofilm penetration for improved PDT efficacy.
  • To assess the impact of fluorination and acid-induced surface charge reversal on micelle stability, drug loading, and antibacterial activity.

Main Methods:

  • Synthesis and characterization of fluorinated (PF-CBMs) and fluorine-free (PC-CBMs) micelles.
  • Evaluation of oxygen-carrying capacity and serum stability of the developed micelles.
  • Assessment of photosensitizer loading, premature release, and cellular uptake.
  • In vitro and in vivo studies to determine the antibiofilm and antibacterial efficacy of PDT using PF-CBMs compared to PC-CBMs.

Main Results:

  • PF-CBMs demonstrated enhanced oxygen transport due to perfluorocarbon content, alleviating hypoxia.
  • Fluorination improved micelle serum stability, increased photosensitizer loading, and reduced premature release.
  • PF-CBMs exhibited acid-induced surface charge reversal, leading to superior biofilm penetration.
  • PDT with PF-CBMs showed significantly enhanced antibacterial and antibiofilm activity in vitro and in vivo compared to PF-CBMs.

Conclusions:

  • Fluorinated micelles (PF-CBMs) effectively overcome hypoxia in PDT by delivering oxygen, thereby enhancing ROS generation.
  • The combination of enhanced oxygen supply, improved stability, and targeted biofilm penetration makes PF-CBMs a promising platform for advanced antibacterial PDT.
  • Surface charge modulation in PF-CBMs further boosts their efficacy in combating bacterial biofilms.
Keywords:
AntibacterialAntibiofilmCharge-switchableFluorinated micellesPhotodynamic therapy

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