Bacteria-Targeting Nanoparticles with Microenvironment-Responsive Antibiotic Release To Eliminate Intracellular Staphylococcus aureus and Associated Infection
Bacteria-Targeting Nanoparticles with Microenvironment-Responsive Antibiotic Release To Eliminate Intracellular Staphylococcus aureus and Associated Infection
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DOI：
10.1021/acsami.7b15678
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发表时间：
2018-05-02
影响因子：
9.5
通讯作者：
Tang, Tingting
中科院分区：
文献类型：
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作者：
Yang, Shengbing;Han, Xiuguo;Tang, Tingting
金黄色葡萄球菌（金黄色葡萄球菌）是危及生命的人类疾病的病原体，每年折磨数百万人。传统的抗生素治疗变得越来越无效，因为金黄色葡萄球菌可以侵入宿主细胞，包括成骨细胞和巨噬细胞，构成一个相对保护的储存库，不受可能导致复发感染的抗生素的影响。我们在此报道了一种独特的细胞内抗生素递送纳米颗粒，它由(i)负载庆大霉素的介孔二氧化硅纳米颗粒（MSN）内核，（ii）受感染的微环境（细菌毒素）响应脂质双分子层表面外壳和（iii）固定在脂质双分子层表面外壳上的细菌靶向肽泛素（UBI29-41）组成。在msn到达目标细胞或组织之前，脂质物质起到阻止药物释放的大门作用，此时它们被细菌毒素降解，迅速释放药物，从而消除有效细菌。我们在细胞外模型中证实了细菌存在下的药物快速释放，并观察到金黄色葡萄球菌的生长在浮游生物和细胞内感染的体外和体内都被有效抑制。感染的成骨前细胞或巨噬细胞中的炎症相关基因表达在抗生素递送纳米颗粒治疗后也显著下调。抗生素递送纳米颗粒在对抗细胞内病原体和消除细胞内细菌感染引起的炎症方面具有优势。
Staphylococcus aureus (S. aureus) is a causative agent in life-threatening human diseases that afflict millions of people annually. Traditional antibiotic treatments are becoming less efficient because S. aureus can invade host cells including osteoblasts and macrophages, constituting a reservoir that is relatively protected from antibiotics that can lead to recrudescent infection. We herein report a unique intracellular antibiotic delivery nanoparticle, which is composed of (i) a mesoporous silica nanoparticle (MSN) core loaded with gentamicin, (ii) an infected microenvironment (bacterial toxin)-responsive lipid bilayer surface shell, and (iii) bacteria-targeting peptide ubiquicidin (UBI29-41) that is immobilized on the lipid bilayer surface shell. The lipid material acts as a gate that prevents drug release before the MSNs reach the target cells or tissue, at which point they are degraded by bacterial toxins to rapidly release the drug, thus eliminating efficient bacteria. We confirm rapid drug release in the presence of bacteria in an extracellular model and observe that S. aureus growth is effectively inhibited both in vitro and in vivo of planktonic and intracellular infection. The inflammation-related gene expression in infected preosteoblast or macrophage is also downregulated significantly after treatment by the antibiotic delivery nanoparticles. The antibiotic delivery nanoparticles offer advantages in fighting intracellular pathogens and eliminating the inflammation caused by intracellular bacterial infections.