南方医科大学学报2025，Vol.45Issue(5)：1013-1022,10.DOI:10.12122/j.issn.1673-4254.2025.05.14
靶向E-选择素的工程化脂质体的设计与炎症靶向评价
Design and inflammation-targeting efficiency assessment of an engineered liposome-based nanomedicine delivery system targeting E-selectin
摘要
Abstract
Objective To develop an E-selectin-targeting nanomedicine delivery system that competitively inhibits E-selectin-neutrophil ligand binding to block neutrophil adhesion to vessels and suppress their recruitment to the lesion sites.Methods Doxorubicin hydrochloride(DOX)-loaded liposomes(IEL-Lip/DOX)conjugated with E-selectin-affinity peptide IELLQARC were developed using a post-insertion method.Two formulations[2-1P:Mol(PC):Mol(DPI)=100:1;2-3P:100:3]were prepared and their modification density and in vitro release characteristics were determined.Their targeting efficacy was assessed in a cell model of LPS-induced inflammation,a mouse model of acute lung injury(ALI),a rat femoral artery model of physical injury-induced inflammation,and a zebrafish model of local inflammation.Results The prepared IEL-Lip/DOX 2-1P and 2-3P had peptide modification densities of 4.76 and 7.57 pmoL/cm2,respectively.Compared with unmodified liposomes,IEL-Lip/DOX exhibited significantly reduced 48-h cumulative release rates at pH 5.5.In the inflammation cell model,IEL-Lip/DOX showed increased uptake by activated inflammatory endothelial cells,and 2-1P exhibited a higher trans-endothelial ability.In ALI mice,the fluorescence intensity of IEL-Lip/Cy5.5 increased significantly in lung tissues by 53.71%[Z-(2-1P)]and 93.41%[Z-(2-3P)],and 2-1P had an increased distribution by 24.19%in the inflammatory lung tissue compared to normal mouse lung tissue.In rat femoral artery models,2-1P had greater injured/normal vessel fluorescence intensity contrast.In the zebrafish models,both 2-1P and 2-3P showed increased aggregation at the site of inflammation.Conclusion This E-selectin-targeting nanomedicine delivery system efficiently targets activated inflammatory endothelial cells to increase drug concentration at the inflammatory site,which sheds light on new strategies for treating neutrophil-mediated inflammatory diseases and practicing the concept of"one drug for multiple diseases".关键词
E-选择素/IEL短肽/盐酸多柔比星脂质体/靶向递送Key words
E-selectin/IEL short peptides/doxorubicin hydrochloride-loaded liposomes/targeted delivery引用本文复制引用
叶雨濛,余波,陆沙沙,周于,丁美红,程桂林..靶向E-选择素的工程化脂质体的设计与炎症靶向评价[J].南方医科大学学报,2025,45(5):1013-1022,10.基金项目
国家自然科学基金(82004250) （82004250）
浙江中医药大学校级科研项目(2021FSYYZY31)Supported by National Natural Science Foundation of China(82004250). （2021FSYYZY31）
