数字农科院2.0

Hypoxia-responsive hybrid nanoparticles loaded with fingolimod and colistin against multidrug-resistant Klebsiella pneumoniae with mature biofilm

文献类型： 外文期刊

作者： Mengting Liu;Xinrui Liu;Tengli Zhang;Yuanqiang Wang;Hong Yao;Xiwang Liu;Zhiguo Fang;Yinglan Yu;Lei Luo

作者机构：

关键词： Biofilm eradication;Colistin;Fingolimod;Hypoxia-responsive hybrid nanoparticle;Multidrug-resistant klebsiella pneumoniae

期刊名称： Asian Journal of Pharmaceutical Sciences

ISSN： 1818-0876

年卷期： 2025 年 20 卷 6 期

页码：

收录情况： SCIE（2025版） ; ; 科技核心（2024版）

摘要： Multidrug-resistant Klebsiella pneumoniae (MDR- KP ) is characterized by high mortality and risk of nosocomial transmission, and biofilm constitutes the primary challenge in the treatment of its implant-associated and refractory pulmonary infections. Notably, the hypoxic microenvironment and the physical barrier of biofilm leading to the increased tolerance of the bacteria to antibiotics. Herein, a hypoxia-responsive hybrid nanoparticle (CHLip@FLD/COL) loaded separately with anti-biofilm candidate fingolimod (FLD) and antibiotic colistin (COL) is achieved targeting antibacterial efficacy against MDR- KP in vitro and in vivo . CHLip@FLD/COL is composed of hybridizing hypoxia-responsive lipids (HLipid) and lipid A targeting materials DSPE-mPEG-COL. HLipid is synthesized by hexadecanedioic acid esterified with nitroimidazole, while DSPE-mPEG is coupling with vector COL via amide reaction. The relative level of extracellular polymeric substances and the NIR-IIb sO2 images of the infection site are used as indicators to establish mature biofilm models. CHLip@FLD/COL readily releases FLD and COL in hypoxic conditions, and its MIC against MDR- KP is only one-sixteenth of that when COL is used alone in vitro . The nanoparticle exhibits bacterial targeting ability and antibacterial effect in the pulmonary infection and biofilm infection mice models. Bacterial loads eliminated by 4 Log10 CFU and 2 Log10 CFU, respectively. The strategy provides a valuable reference for the treatment of refractory infections caused by MDR- KP .

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