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

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Vol. 9; no. 43; pp. 8951 - 8961
• Main Authors: Qiao, Jing, Cui, Shuolin, Xiong, May P
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 10.11.2021
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibiotics; Bacteria; Block copolymers; Controlled release; Drug delivery; Drug Delivery Systems; Encapsulation; Energy transfer; Fluorescence; Fluorescence resonance energy transfer; Fluorescent Dyes - chemistry; Fluorescent Dyes - pharmacology; Hydrogen peroxide; Hydrophobic and Hydrophilic Interactions; Hydrophobicity; Immune system; Infections; Inflammatory diseases; Intracellular; Macrophages; Micelles; Microbial Sensitivity Tests; Molecular Structure; Nanoparticles; Oxidation; Particle Size; Phagocytes; Polyethylene glycol; Reactive oxygen species; Reactive Oxygen Species - metabolism; Rifampin; Self-assembly; Staphylococcal Infections - drug therapy; Staphylococcal Infections - metabolism; Staphylococcus aureus - drug effects; Surface Properties
• ISSN: 2050-750X; 2050-7518; 2050-7518
• DOI: 10.1039/d1tb01702k

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 H O 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.