Biomimetic Metal–Organic Framework Gated Nanoplatform for Sonodynamic Therapy against Extensively Drug Resistant Bacterial Lung Infection

作者：Jianling Huang, Xiuwen Hong, Sixi Chen, Yucong He, Lixu Xie, Fenglin Gao, Chenghua Zhu, Xiao Jin, Haihao Yan, Yongxia Ye, Mingyue Shao, Xingran Du, Ganzhu Feng · 发表于：Advanced Science · 年份：2024 · DOI：10.1002/advs.202402473 · 被引用次数：35 · 研究领域：Nanoplatforms for cancer theranostics、Inhalation and Respiratory Drug Delivery、Ultrasound and Hyperthermia Applications

Abstract Novel antimicrobial strategies are urgently needed to treat extensively drug‐resistant (XDR) bacterial infections due to the high mortality rate and lack of effective therapeutic agents. Herein, nanoengineered human umbilical cord mesenchymal stem cells (hUC‐MSCs), named PMZMU, are designed as a sonosensitizer for synergistic sonodynamic‐nano‐antimicrobial therapy against gram‐negative XDR bacteria. PMZMU is composed of a bacterial targeting peptide (UBI 29‐41 ) modified hUC‐MSCs membrane (MSCm), a sonosensitizer meso‐tetra(4‐car‐boxyphenyl) porphine doped mesoporous organo‐silica nanoparticle and an acidity‐responsive metal–organic framework ZIF‐8. This innovative formulation enables efficient loading of polymyxin B, reduces off‐target drug release, increases circulation and targeting efficacy, and generates reactive oxygen species upon ultrasound irradiation. PMZMU exhibits remarkable in vitro inhibitory activity against four XDR bacteria: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa (PA), and Escherichia coli . Taking advantage of the bacterial targeting ability of UBI 29‐41 and the inflammatory chemotaxis of hUC‐MSC, PMZMU can be precisely delivered to lung infection sites thereby augmenting polymyxin B concentration. PMZMU‐mediated sonodynamic therapy significantly reduces bacterial burden, relieves inflammatory damage by promoting the polarization of macrophages toward M 2 phenotype, and improves survival rates without introducing adve...