Bacterial toxin-triggered release of antibiotics from capsosomes protects a fly model from lethal methicillin-resistant Staphylococcus aureus (MRSA) infection
Author(s)
Type
Journal Article
Abstract
Antibiotic resistance is a severe global health threat and hence demands rapid action to develop novel therapies, including microscale drug delivery systems. Herein, a hierarchical microparticle system is developed to achieve bacteria-activated single- and dual-antibiotic drug delivery for preventing methicillin-resistant Staphylococcus aureus (MRSA) bacterial infections. The designed system is based on a capsosome structure, which consists of a mesoporous silica microparticle coated in alternating layers of oppositely charged polymers and antibiotic-loaded liposomes. The capsosomes are engineered and shown to release their drug payloads in the presence of MRSA toxins controlled by the Agr quorum sensing system. MRSA-activated single drug delivery of vancomycin and synergistic dual delivery of vancomycin together with an antibacterial peptide successfully kills MRSA in vitro. The capability of capsosomes to selectively deliver their cargo in the presence of bacteria, producing a bactericidal effect to protect the host organism, is confirmed in vivo using a Drosophila melanogaster MRSA infection model. Thus, the capsosomes serve as a versatile multidrug, subcompartmentalized microparticle system for preventing antibiotic-resistant bacterial infections, with potential applications to protect wounds or medical device implants from infections.
Date Issued
2022-07
Date Acceptance
2022-04-13
Citation
Advanced Healthcare Materials, 2022, 11 (14), pp.1-14
ISSN
2192-2640
Publisher
Wiley-VCH Verlag
Start Page
1
End Page
14
Journal / Book Title
Advanced Healthcare Materials
Volume
11
Issue
14
Copyright Statement
© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Sponsor
Wellcome Trust
Wellcome Trust
Commission of the European Communities
Royal Academy Of Engineering
Identifier
https://onlinelibrary.wiley.com/doi/10.1002/adhm.202200036
Grant Number
207467/Z/17/Z
209121/Z/17/Z
838183
CIET2021\94
Subjects
Science & Technology
Technology
Engineering, Biomedical
Nanoscience & Nanotechnology
Materials Science, Biomaterials
Engineering
Science & Technology - Other Topics
Materials Science
antibiotic delivery
capsosomes
microparticles
MRSA
vancomycin
DROSOPHILA-MELANOGASTER
ANTIMICROBIAL PEPTIDES
COMBINATION THERAPY
DELIVERY-SYSTEMS
ALPHA-TOXIN
VANCOMYCIN
MICROSPHERES
NANOPARTICLES
PREVALENCE
EXPRESSION
MRSA
antibiotic delivery
capsosomes
microparticles
vancomycin
Animals
Anti-Bacterial Agents
Bacterial Toxins
Drosophila melanogaster
Methicillin-Resistant Staphylococcus aureus
Microbial Sensitivity Tests
Staphylococcal Infections
Vancomycin
Animals
Drosophila melanogaster
Staphylococcal Infections
Vancomycin
Bacterial Toxins
Anti-Bacterial Agents
Microbial Sensitivity Tests
Methicillin-Resistant Staphylococcus aureus
0304 Medicinal and Biomolecular Chemistry
0903 Biomedical Engineering
1004 Medical Biotechnology
Publication Status
Published
Date Publish Online
2022-04-28