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Programmable antibiotic delivery to combat methicillin-resistant Staphylococcus aureus through precision therapy
- Source :
- Journal of Controlled Release. 321:710-717
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- The rapid dissemination of life-threatening multidrug-resistant bacterial pathogens calls for the development of new antibacterial agents and alternative strategies. The virulence factor secreted by bacteria plays a crucial role in the sophisticated processes during infections. Inspired by the unique capacity of many bacteria inducing clotting of plasma to initiate colonization, we propose a programmable antibiotic delivery system for precision therapy using methicillin-resistant S. aureus (MRSA) as a model. Coagulase utilized by MRSA to directly cleave fibrinogen into fibrin, is an ideal target not only for tracking bacterial status but for triggering the collapse of fibrinogen functionalized porous microspheres. Subsequently, staphylokinase, another virulence factor of MRSA, catalyzed hydrolysis of fibrin to further release the encapsulated antibiotics from microspheres. Our sequential triggered-release system exhibits high selectivity to distinguish live or dead MRSA from other pathogenic bacteria. Furthermore, such programmable microspheres clear 99% MRSA in 4 h, and show increased efficiency in a wound healing model in rats. Our study provides a programmable drug delivery system to precisely target bacterial pathogens using their intrinsic enzymatic cascades. This programmable platform with reduced selective stress of antibiotics on microbiota sheds light on the potential therapy for future clinical applications.
- Subjects :
- Methicillin-Resistant Staphylococcus aureus
medicine.drug_class
Antibiotics
Pharmaceutical Science
Microbial Sensitivity Tests
02 engineering and technology
medicine.disease_cause
Virulence factor
Microbiology
03 medical and health sciences
Drug Delivery Systems
Animals
Medicine
Precision Medicine
030304 developmental biology
0303 health sciences
biology
business.industry
Pathogenic bacteria
Staphylokinase
Staphylococcal Infections
021001 nanoscience & nanotechnology
biology.organism_classification
Methicillin-resistant Staphylococcus aureus
Anti-Bacterial Agents
Rats
Drug delivery
Coagulase
0210 nano-technology
business
Bacteria
Subjects
Details
- ISSN :
- 01683659
- Volume :
- 321
- Database :
- OpenAIRE
- Journal :
- Journal of Controlled Release
- Accession number :
- edsair.doi.dedup.....a5dcf4ec8d9c5e1ae06787e30dd83391