期刊
ADVANCED FUNCTIONAL MATERIALS
卷 31, 期 35, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.202103442
关键词
bacterial infections; mesoporous silica nanoparticles; outer membrane vesicles; rifampicin; targeted antibiotic delivery
类别
资金
- Institute of Bioengineering and Bioimaging (Biomedical Research Council, Agency for Science, Technology and Research, Singapore)
- National Natural Science Foundation of China [81803481, 81830103, 31900982, 52072418]
- Science, Technology and Innovation Commission of Shenzhen Municipality [JCYJ20190807151807459]
- Fundamental Research Funds for the Central Universities of China [20ykpy123, 19ykpy142]
This study introduces a biomimetic nanodelivery system consisting of outer membrane vesicles isolated from E. coli as shell and rifampicin-loaded mesoporous silica nanoparticles as core, aiming to enhance bacterial targeting and uptake, thus improving antimicrobial activity against Gram-negative bacteria.
The efficacy of conventional antibiotics therapeutics has declined rapidly due to the emerged antibiotic resistance. There is an urgent need to develop novel approaches to address the problem of antibiotic shortage, particularly for Gram-negative bacteria. Herein, a biomimetic nanodelivery system is proposed to enhance the bacterial targeting and uptake of rifampicin (Rif), a traditional antibiotic but not effective against Gram-negative bacteria. The biomimetic nanodelivery system (Rif@MSN@OMV) is composed of outer membrane vesicles (OMVs) isolated from E. coli as shell and rifampicin-loaded mesoporous silica nanoparticles (MSNs) as core. The OMVs greatly improve the uptake of MSNs in E. coli, but not in Gram-positive bacteria S. aureus, owing to the homotypic targeting function of the OMVs. The Rif@MSN@OMV exhibits enhanced antimicrobial activity against E. coli and completely eradicates bacteria at an equivalent rifampicin concentration (4 mu g mL(-1)) while free rifampicin shows weak bactericidal activity. Meanwhile, the Rif@MSN@OMV maintains good biocompatibility both in vitro and in vivo. More importantly, the Rif@MSN@OMV elevates survival rate of infected mice and reduces bacterial load in intraperitoneal fluid and organs. Overall, the OMVs-coated nanodelivery system provides a novel strategy to improve the antimicrobial efficacy of conventional antibiotic or repurpose drugs for treatment of Gram-negative bacterial infections.
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