巨噬细胞负载Fe_(3)O_(4)@PLGA纳米颗粒触发智能催化功能杀死多重耐药大肠杆菌  

Biomimetic Macrophage-Fe3O4@PLGA Particle-Triggered Intelligent Catalysis for Killing Multidrug-Resistant Escherichia coli

作　　者：Jieni Fu Xiangmei Liu Zhaoyang Li Yufeng Zheng Yu Zhang Hui Jiang Yanqin Liang Shengli Zhu Zhenduo Cui Shuilin Wu 

机构地区：[1]Key Laboratory of Advanced Ceramics and Machining Technology of the Ministry of Education,School of Materials Science and Engineering,Tianjin University,Tianjin 300401,China [2]School of Materials Science and Engineering,Peking University,Beijing 100871,China [3]School of Health Sciences and Biomedical Engineering,Hebei University of Technology,Tianjin 300401,China [4]Department of Orthopedics,Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510080,China

出　　处：《Engineering》2024年第3期174-186,共13页工程（英文）

基　　金：supported by the China National Funds for Distinguished Young Scientists (51925104);the National Natural Science Foundation of China (NSFC) (51871162 and 52173251);NSFC-Guangdong Province Joint Program (U21A2084);the Central Guidance on Local Science and Technology Development Fund of Hebei Province (226Z1303G).

摘　　要：Infections with multidrug-resistant(MDR)Gram-negative bacteria,such as MDR Escherichia coli(E.coli),remain a challenge due to the lack of safe antibiotics and high fatality rates under anti-infection therapies.This work presents a form of biomimetic intelligent catalysis inspired by the selective biocatalytic property of macrophages(MΦs),consisting of an intelligent controlling center(a living MΦ)and a Fenton reaction catalyst(Fe_(3)O_(4)@poly(lactic-co-glycolic acid)(PLGA)nanoparticles)for killing MDR E.coli without harming normal cells.The MΦ-Fe_(3)O_(4)@PLGA particles(i.e.,the intelligent catalysis particles)exhibit selective biocatalysis activity toward MDR E.coli by producing H_(2)O_(2) and lipid droplets(LDs).This process activates the lipid metabolism and glycan biosynthesis and metabolism pathways based on the result of RNA sequencing data analysis.The H_(2)O_(2) further reacts with Fe_(3)O_(4)@PLGA to form highly toxic hydroxyl radicals(·OH),while the LDs contain antimicrobial peptides and can target MDR E.coli.The highly toxicOH and antimicrobial peptides are shown to combat with MDR E.coli,such that the antibacterial efficiency of the MΦ-Fe_(3)O_(4)@PLGA particles against MDR E.coli is 99.29%±0.31%in vitro.More importantly,after several passages,the intelligent catalysis function of the MΦ-Fe_(3)O_(4)@PLGA particles is well maintained.Hence,the concept of biomimetic intelligent catalysts displays potential for treating diseases other than infections.

关 键 词：Multidrug-resistant Escherichia coli Macrophage-Fe_(3)O_(4)@PLGA particles Biomimetic intelligent catalysis 

分 类 号：R318[医药卫生—生物医学工程]