Exosome-encapsulated antibiotic against intracellular infections of methicillin-resistant <em>Staphylococcus aureus</em>

Abstract

BackgroundStaphylococcus aureus survival inside phagocytes is considered to provide a reservoir of bacteria that are relatively protected from antibiotics, thus enabling long-term colonization of the host and explaining clinical failures and relapses after antibiotic therapy.PurposeThe objective of this study was to develop a nanovesicle using exosomes loaded with linezolid to overcome intracellular infections by pathogenic bacteria.MethodsExosomes were collected from the culture supernatants of RAW 264.7 cells. Their size distribution and zeta potential were characterized by dynamic light scattering, their morphology was characterized by transmission electron microscopy, and their protein content (CD63 and Flotillin 1) was assessed by Western blotting. Linezolid was incorporated into exosomes by co-incubation at 37°C and it’s accumulation in RAW264.7 cells and release in vitro were determined by high performance liquid chromatography. The intracellular bactericidal effect was evaluated in methicillin-resistant S. aureus (MRSA)-infected macrophages in vitro and MRSA peritonitis model in vivo.ResultsWe prepared a nanoformulation of the antibiotic linezolid using exosomes harvested from mouse RAW264.7 macrophages. The exosomal formulation of linezolid was more effective against intracellular MRSA infections in vitro and in vivo than the free linezolid. Our data also showed no signs of cytotoxicity in macrophages.ConclusionExosomes provide an effective alternative for intracellular antibiotic delivery of antibiotic that is efficacious, cost-effective, and safe. This regimen can be viewed as a potential antimicrobial agent for use against intracellular infections.

Repurposing Antiviral Protease Inhibitors Using Extracellular Vesicles for Potential Therapy of COVID-19

“…In addition, new techniques may be developed to encapsulate these EVs in another biomimetic nanostructure, e.g., liposomes, for the delivery of EV-encapsulated drugs [86]. EVs have been shown to deliver their biological cargos via multiple mechanisms, such as the fusion of EVs with recipient cells and engulfing of EVs by a variety of recipient cells [87]. Although the mechanism of drug delivery to recipient cells by EVs has not been fully studied, it is likely that a similar mechanism to deliver drug-encapsulated EVs may also exist.…”

“…EVs were recently shown to maintain stability under autoclave temperatures [88]. More importantly, EV-based drug products were reported to be eligible for sterile filtration using filters with 200 nm pore sizes [87]. Both autoclave and sterile filtration are FDA-approved methods for sterile drug preparation.…”

Advances in Exosomes‐Based Drug Delivery Systems

“…The results demonstrate that linezolid incorporated in exosomes significantly inhibited MRSA infection in vivo with a low cytotoxicity to macrophages. [174] Also exosomes have been proposed as vaccines due to their ability to prepare the immune system to kill invading pathogens. [169,175] Exosomes secreted by antibiotic resistant Pseudomonas or Helminth parasites may potentially be used as vaccine vehicles for the promotion of immunity against these types of organisms.…”

<p>Near-Infrared Laser-Triggered, Self-Immolative Smart Polymersomes for in vivo Cancer Therapy</p>

“…17,18 However, the ability to encapsulate only hydrophobic drugs and lower drug loadings limit their further applications. Therefore, continuing our efforts in searching for effective therapeutics, [19][20][21][22][23] we designed an oxidative responsive nanosystem mediated by NIR, which exhibited combination effect of PDT and chemotherapy. As shown in Scheme 1, a suitable proportion of PPS-PEG was used as a primary material for the nanosystem.…”