Bacteria-Targeted Supramolecular Photosensitizer Delivery Vehicles for Photodynamic Ablation Against Biofilms

Macromol Rapid Commun. 2019 Feb;40(4):e1800763. doi: 10.1002/marc.201800763. Epub 2018 Nov 30.

Abstract

Photodynamic therapy (PDT) is believed to be a potent method for biofilm treatments. However, undesired damage to normal cells may be caused due to the nonselective nature of PDT. Therefore, targeted PDT is preferred on one hand to enhance antimicrobial effects and on the other hand to reduce cytotoxicity to normal cells. For this purpose, novel bacteria-targeted photosensitizer delivery micelles are fabricated, taking advantage of α-cyclodextrin (α-CD)/polyethylene glycol (PEG) supramolecular assembly. Hydrophilic antimicrobial peptide (AMP) Magainin I is covalently bound with PEG, working as a bacterial targeting group as well as the stabilizing shell of the supramolecular micelles. Photosensitizer Chlorin e6 (Ce6) is grafted onto α-CD. The micelles exhibit excellent bacterial targeting effects. Compared to α-CD-Ce6, the supramolecular micelles possess enhanced biofilm killing ability against Gram (-) Pseudomonas aeruginosa biofilms and Gram (+) methicillin-resistant Staphylococcus aureus (MRSA) biofilms while reducing cytotoxicity to NIH/3T3 model cells.

Keywords: antimicrobial peptides; biofilms; cytocompatibility; photodynamic therapy; targets.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects
  • Cell Survival / drug effects
  • Humans
  • Macromolecular Substances / chemical synthesis
  • Macromolecular Substances / chemistry
  • Macromolecular Substances / pharmacology
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Mice
  • Micelles
  • Microbial Sensitivity Tests
  • Microscopy, Fluorescence
  • Molecular Structure
  • NIH 3T3 Cells
  • Optical Imaging
  • Photochemotherapy
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Pseudomonas aeruginosa / drug effects*

Substances

  • Anti-Bacterial Agents
  • Macromolecular Substances
  • Micelles
  • Photosensitizing Agents