首页|In situ visualization of the cellular uptake and sub-cellular distribution of mussel oligosaccharides

In situ visualization of the cellular uptake and sub-cellular distribution of mussel oligosaccharides

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  • 国家科技期刊平台
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  • NSTL
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Unlike chemosynthetic drugs designed for specific molecular and disease targets,active small-molecule natural products typically have a wide range of bioactivities and multiple targets,necessitating extensive screening and development.To address this issue,we propose a strategy for the direct in situ micro-dynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of action.As a proof-of-concept,we investigated the behavior of mussel oligosaccharide(MOS-1)by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured cells.We recorded the entire dynamic process of the localization of fluorescein isothiocyanate(FITC)-MOS-1 to the lysosomes and visualized the distribution of the drug within the cell.Remarkably,lysosomes containing FITC-MOS-1 actively recruited lipid droplets,leading to fusion events and increased cellular lipid consumption.These drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related diseases.Furthermore,in a high-fat HepG2 cell model and in high-fat diet-fed apolipoprotein E(ApoE)-/-mice,MOS-1 significantly promoted triglyceride degradation,reduced lipid droplet accumulation,lowered serum triglyceride levels,and mitigated liver damage and steatosis.Overall,our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase,as this methodology contributes to the rapid identification of drug indications.Collectively,this methodology is significant for the screening and development of selective small-molecule drugs,and is expected to expedite the identification of candidate molecules with me-dicinal effects.

Cellular imagingFluorescence labelingMussel oligosaccharideLipid metabolism

Zhenjie Yu、Huarong Shao、Xintian Shao、Linyan Yu、Yanan Gao、Youxiao Ren、Fei Liu、Caicai Meng、Peixue Ling、Qixin Chen

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Key Laboratory for Biotechnology Drugs of National Health Commission,School of Pharmaceutical Sciences & Institute of Materia Medica,Medical Science and Technology Innovation Center,Shandong First Medical University & Shandong Academy of Medical Sciences,Jinan,250117,China

Key Laboratory of Biopharmaceuticals,Engineering Laboratory of Polysaccharide Drugs,National-Local Joint Engineering Laboratory of Polysaccharide Drugs,Shandong Academy of Pharmaceutical Science,Jinan,250101,China

Shenzhen Research Institute of Xiamen University,Shenzhen,Guangdong,518057,China

School of Life Sciences,Medical Science and Technology Innovation Center,Shandong First Medical University & Shandong Academy of Medical Sciences,Jinan,250117,China

School of Pharmaceutical Sciences,Shandong University,Jinan,250101,China

Departments of Diagnostic Radiology,Surgery,Chemical and Biomolecular Engineering,and Biomedical Engineering,Yong Loo Lin School of Medicine and Faculty of Engineering,National University of Singapore,Singapore,119074,Singapore

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2024

10.1016/j.jpha.2023.12.022

药物分析学报(英文)
西安交通大学

药物分析学报(英文)

影响因子：0.244
ISSN：2095-1779
年,卷(期)：2024.14(6)