Lung-targeted polyzwitterionic lipid nanoparticles for effective treatment of lung inflammation

IF 10.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Science China Chemistry Pub Date : 2025-01-02 DOI:10.1007/s11426-024-2295-8

Wen Zhang, Jiaxin Li, Nan Wang, Muzi Li, Chen Peng, Xinyue Zhang, Guanghui Ouyang, Yan Li

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引用次数: 0

Abstract

Lipid nanoparticles (LNPs) are non-viral nucleic acid delivery systems that show great potential in vaccine development and disease treatment. Although LNPs are particularly advantageous for in vivo delivery, the wide application of LNPs is impeded as their systemic delivery of nucleic acid drugs to extrahepatic tissues remains highly challenging. To address this issue, we developed lung-targeted polyzwitterionic LNPs with zwitterionic polymer poly(2-methyacryloyloxyethyl phosphorylcholine) (PMPC) modified 1,2-dimyristoyl-sn-glycerol lipid for the delivery of small interfering RNA (siRNA). Three libraries with 90 PMPC-LNPs@siRNA were established. The polyzwitterionic PMPC-LNPs had high siRNA encapsulation efficiency of about 90%. The findings revealed that polyzwitterionic PMPC-LNPs@siRNA absorbed protein corona with the main component of Vitronectin, mediating lung-targeted delivery of siRNA. With good cellular uptake and endo/lysosomal escape ability, in vitro and in vivo studies demonstrated that polyzwitterionic PMPC-LNPs with siRNA against tumor necrosis factor-α (TNF-α) could significantly down-regulate the TNF-α in mRNA and protein levels, and improved the pathological features of lung inflammation. Polyzwitterionic PMPC-LNPs@siRNA achieved safe and efficient treatment of lung inflammation. Therefore, this work offered a promising siRNA therapeutic approach for lung diseases.

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来源期刊

Science China Chemistry CHEMISTRY, MULTIDISCIPLINARY-

CiteScore

14.40

自引率

7.30%

发文量

3787

审稿时长

2.2 months

期刊介绍： Science China Chemistry, co-sponsored by the Chinese Academy of Sciences and the National Natural Science Foundation of China and published by Science China Press, publishes high-quality original research in both basic and applied chemistry. Indexed by Science Citation Index, it is a premier academic journal in the field. Categories of articles include: Highlights. Brief summaries and scholarly comments on recent research achievements in any field of chemistry. Perspectives. Concise reports on thelatest chemistry trends of interest to scientists worldwide, including discussions of research breakthroughs and interpretations of important science and funding policies. Reviews. In-depth summaries of representative results and achievements of the past 5–10 years in selected topics based on or closely related to the research expertise of the authors, providing a thorough assessment of the significance, current status, and future research directions of the field.