Design and inflammation-targeting efficiency assessment of an engineered liposome-based nanomedicine delivery system targeting E-selectin
YE Yumeng
YU Bo
LU Shasha
ZHOU Yu
DING Meihong
CHENG Guilin
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".
Keywords：E-selectinIEL short peptidesdoxorubicin hydrochloride-loaded liposomestargeted delivery
Publication Date：2025-05-20
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：10( 1013-1022 )