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首页> 外文期刊>ACS nano >Surface-Adaptive, Antimicrobially Loaded, Micellar Nanocarriers with Enhanced Penetration and Killing Efficiency in Staphylococcal Biofilms
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Surface-Adaptive, Antimicrobially Loaded, Micellar Nanocarriers with Enhanced Penetration and Killing Efficiency in Staphylococcal Biofilms

机译：在葡萄球菌生物膜中具有增强的穿透力和杀灭效率的表面适应性，抗微生物负载的胶束纳米载体

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摘要

Biofilms cause persistent bacterial infections and are extremely recalcitrant to antimicrobials, due in part to reduced penetration of antimicrobials into biofilms that allows bacteria residing in the depth of a biofilm to survive antimicrobial treatment. Here, we describe the preparation of surface-adaptive, Triclosan-loaded micellar nanocarriers showing (1) enhanced biofilm penetration and accumulation, (2) electrostatic targeting at acidic pH toward negatively charged bacterial cell surfaces in a biofilm, and (3) antimicrobial release due to degradation of the micelle core by bacterial lipases. First, it was established that mixed-shell-polymeric-micelles (MSPM) consisting of a hydrophilic poly(ethylene glycol) (PEG)-shell and pH-responsive poly(beta-amino ester) become positively charged at pH 5.0, while being negatively charged at physiological pH. This is opposite to single-shell-polymeric-micelles (SSPM) possessing only a PEG-shell and remaining negatively charged at pH 5.0. The stealth properties of the PEG-shell combined with its surface adaptive charge allow MSPMs to penetrate and accumulate in staphylococcal biofilms, as demonstrated for fluorescent Nile red loaded micelles using confocal-laser-scanning-microscopy. SSPMs, not adapting a positive charge at pH 5.0, could not be demonstrated to penetrate and accumulate in a biofilm. Once micellar nanocarriers are bound to a staphylococcal cell surface, bacterial enzymes degrade the MSPM core to release its antimicrobial content and kill bacteria over the depth of a biofilm. This constitutes a highly effective pathway to control blood-accessible staphylococcal biofilms using antimicrobials, bypassing biofilm recalcitrance to antimicrobial penetration.
机译：生物膜引起持续的细菌感染，并且对抗菌剂极为顽固，部分原因是由于抗菌剂对生物膜的渗透性降低，使驻留在生物膜深处的细菌能够经受抗菌治疗。在这里，我们描述了表面适应性，三氯生负载的胶束纳米载体的制备，这些载体显示（1）增强的生物膜渗透和累积，（2）在酸性pH下朝向生物膜中带负电的细菌细胞表面的静电靶向，以及（3）抗菌释放由于细菌脂肪酶降解了胶束核心。首先，确定了由亲水性聚乙二醇（PEG）-壳和pH响应型聚（β-氨基酯）组成的混合壳聚合物胶束（MSPM）在pH 5.0时带正电，而在生理pH下带负电。这与仅具有PEG壳并在pH 5.0时带负电的单壳聚合物胶束（SSPM）相反。 PEG壳的隐身特性与其表面适应性电荷相结合，使MSPM能够渗透并积聚在葡萄球菌生物膜中，如使用共聚焦激光扫描显微镜观察的荧光尼罗红胶束所证明的那样。无法证明在pH 5.0下不能适应正电荷的SSPM会渗透并积聚在生物膜中。一旦胶束纳米载体与葡萄球菌细胞表面结合，细菌酶就会降解MSPM核心，释放其抗菌成分，并在生物膜的整个深度杀死细菌。这构成了一种高效的途径，使用抗菌剂来控制血液可及的葡萄球菌生物膜，从而绕过生物膜对抗菌剂渗透的顽固性。

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