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ROS-sensitive micelles for controlled delivery of antibiotics to combat intracellular Staphylococcus aureus-associated infections.

Abstract
Bacteria can evade the immune system once they are engulfed by phagocytic host cells. This protects them against the bactericidal action of antibiotics and allows the infection to remain latent or to recur. Reactive oxygen species (ROS)-related stress has been implicated in various pathological conditions such as inflammatory diseases involving infections of host cells and can serve as a useful trigger for intracellular controlled drug delivery. We herein report on a fluorescent ROS-sensitive intracellular antibiotic delivery nanoparticle for encapsulation of rifampin (RIF) based on the principles of Förster Resonance Energy Transfer (FRET) that is capable of ratiometrically sensing H2O2 levels and monitoring the drug release process. The fluorescent micelles (MFs) are formed through the self-assembly of amphiphilic diblock copolymers consisting of a poly(ethylene glycol) (PEG) segment and a fluorescent oxidation-responsive hydrophobic phenylboronic pinacol ester (PBA) block. Specifically, MFs could encapsulate the model antibiotic RIF (MF/RIF) and ROS-triggered controlled release of RIF within infected macrophages (where ROS levels are elevated) improved the elimination of intracellular bacteria compared to MF or RIF alone. This antibiotic delivery system may be especially effective at fighting intracellular pathogens that have managed to evade the immune system and could minimize exposure of normal cells and tissues to high drug concentrations.
AuthorsJing Qiao, Shuolin Cui, May P Xiong
JournalJournal of materials chemistry. B (J Mater Chem B) Vol. 9 Issue 43 Pg. 8951-8961 (11 10 2021) ISSN: 2050-7518 [Electronic] England
PMID34606554 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Anti-Bacterial Agents
  • Fluorescent Dyes
  • Micelles
  • Reactive Oxygen Species
Topics
  • Anti-Bacterial Agents (chemistry, pharmacology)
  • Drug Delivery Systems
  • Fluorescent Dyes (chemistry, pharmacology)
  • Hydrophobic and Hydrophilic Interactions
  • Micelles
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Particle Size
  • Reactive Oxygen Species (metabolism)
  • Staphylococcal Infections (drug therapy, metabolism)
  • Staphylococcus aureus (drug effects)
  • Surface Properties

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