文献类型：期刊文献

英文题名：Bacteria-Targeting Nanoparticles with Microenvironment-Responsive Antibiotic Release To Eliminate Intracellular Staphylococcus aureus and Associated Infection

作者：Yang, Shengbing[1];Han, Xiuguo[1];Yang, Ying[1];Qiao, Han[1];Yu, Zhifeng[1];Liu, Yang[2];Wang, Jing[2];Tang, Tingting[1]

机构：[1]Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Shanghai Key Lab Orthopaed Implants,Dept Orthopae, 639 Zhizaoju Rd, Shanghai 200011, Peoples R China;[2]East China Univ Sci & Technol, Minist Educ, Key Lab Ultrafine Mat, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2018

卷号：10

期号：17

起止页码：14299

外文期刊名：ACS APPLIED MATERIALS & INTERFACES

收录：;EI(收录号：20181905153576);WOS:【SCI-EXPANDED(收录号:WOS:000431723400011)】；

基金：This work was funded by the National Key R&D Program (2016YFC1102100), National Natural Science Foundation of China (81672205), Biomedical Engineering Crossover Project of Shanghai JiaoTong University (YG2014ZD01), the grant from the National Natural Science Foundation of China (81401819), and the China Postdoctoral Science Foundation (2015M571574).

语种：英文

外文关键词：nanoparticles; targeting; intracellular infection; bacterial toxin responsive; mesoporous silica nanoparticles

摘要：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.