In situ visualization of the cellular uptake and sub-cellular distribution of mussel oligosaccharidesOA
In situ visualization of the cellular uptake and sub-cellular distribution of mussel oligosaccharides
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.
Zhenjie Yu;Qixin Chen;Huarong Shao;Xintian Shao;Linyan Yu;Yanan Gao;Youxiao Ren;Fei Liu;Caicai Meng;Peixue Ling
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,ChinaKey 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||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,SingaporeKey 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,ChinaSchool of Life Sciences,Medical Science and Technology Innovation Center,Shandong First Medical University & Shandong Academy of Medical Sciences,Jinan,250117,ChinaKey Laboratory of Biopharmaceuticals,Engineering Laboratory of Polysaccharide Drugs,National-Local Joint Engineering Laboratory of Polysaccharide Drugs,Shandong Academy of Pharmaceutical Science,Jinan,250101,China||School of Pharmaceutical Sciences,Shandong University,Jinan,250101,ChinaKey Laboratory of Biopharmaceuticals,Engineering Laboratory of Polysaccharide Drugs,National-Local Joint Engineering Laboratory of Polysaccharide Drugs,Shandong Academy of Pharmaceutical Science,Jinan,250101,China
Cellular imagingFluorescence labelingMussel oligosaccharideLipid metabolism
《药物分析学报（英文）》 2024 (006)
840-850 / 11
This work was financially supported by Shandong Province Key R&D Program,China(Major Technological Innovation Project)(Grant No.:2021CXGC010501),Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine,China(Grant No.:CACM-2023-QNRC1-02),the National Natural Science Foun-dation of China(Grant Nos.:22107059,22007060,and 82302743),the Natural Science Foundation of Shandong Province,China(Grant Nos.:ZR2022QH304,ZR2021QH057,and ZR2020QB166),the Pro-gram for Youth Innovation Technology in Colleges and Universities of Shandong Province of China(Grant No.:2021KJ035),Taishan Scholars Program,China(Grant Nos.:TSQN202211221 and TSPD20181218),Shandong Science Fund for Excellent Young Scholars,China(Grant No.:ZR2022YQ66),Shandong Province Traditional Chinese Medicine Science and Technology Project,China(Grant No.:Q-2023059),Shenzhen Basic Research Project,China(Grant No.:JCYJ20190809160209449),the General Project of Shandong Natural Science Foundation,China(Grant No.:ZR2021MH341),and Jinan Innovation Team Project of Colleges and Universities,China(Grant No.:2021GXRC072).
评论