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Folic acid modified mesoporous silica nanoparticles with pH-responses enhance Amp anti-drug-resistant bacteria by overcoming efflux pump systems

Abstract

Efflux pump system-mediated bacterial multidrug resistance is one of the main causes of antibiotic failure. Therefore, it is necessary to develop a novel nanocarrier which can effectively inhibit drug-resistant bacteria by increasing the intake and retention time of antibiotics. Herein, we constructed a pH-responsive nanocarrier (MSN@FA@CaP@FA) which covered double folic acid (FA) and calcium phosphate (CaP) on the surface of mesoporous silica (MSN) by electrostatic attraction and biomineralization respectively. Afterwards, the nanocomposites loading the ampicillin (Amp) effectively increased the uptake and reduced the efflux effect in Escherichia coli (E.coli) and Staphylococcus aureus (S.aureus) by the specific targeting of FA. Moreover, Amp-MSN@FA@CaP@FA can specifically transport Amp to the bacterial infection site. Similarly, in antibacterial experiments revealed that Amp-MSN@FA@CaP@FA can significantly enhance the activity of Amp for inhibiting drug-resistant bacteria and without producing drug resistance. Additionally, Amp-MSN@FA@CaP@FA could reduced the content of protein and inhibited the protein activity in drug-resistant bacteria, so that it destructed the bacterial membrane and led to the bacteria death. While in vivo antibacterial experiments Amp-MSN@FA@CaP@FA effectively reduced the mortality of drug-resistant E.coli infection and promoted wound healing of drug-resistant S.aureus infection. In summary, Amp-MSN@FA@CaP@FA has a potential applying prospect in sustained-release nanostructures and inhibit drug-resistant bacteria.

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Publication details

The article was received on 06 Mar 2018, accepted on 09 May 2018 and first published on 16 May 2018


Article type: Paper
DOI: 10.1039/C8BM00262B
Citation: Biomater. Sci., 2018, Accepted Manuscript
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    Folic acid modified mesoporous silica nanoparticles with pH-responses enhance Amp anti-drug-resistant bacteria by overcoming efflux pump systems

    X. Chen, Y. Liu, A. Lin, N. Huang, L. Long, Y. Gang and J. Liu, Biomater. Sci., 2018, Accepted Manuscript , DOI: 10.1039/C8BM00262B

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