Design and inflammation-targeting efficiency assessment of an engineered liposome-based nanomedicine delivery system targeting E-selectin.
10.12122/j.issn.1673-4254.2025.05.14
- Author:
Yumeng YE
1
;
Bo YU
2
;
Shasha LU
1
;
Yu ZHOU
1
;
Meihong DING
1
;
Guilin CHENG
1
Author Information
1. School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
2. School of Medicine, Shaoxing University, Shaoxing 312000, China.
- Publication Type:Journal Article
- Keywords:
E-selectin;
IEL short peptides;
doxorubicin hydrochloride-loaded liposomes;
targeted delivery
- MeSH:
Animals;
Liposomes;
Rats;
Nanomedicine;
E-Selectin;
Drug Delivery Systems;
Inflammation/drug therapy*;
Mice;
Doxorubicin/analogs & derivatives*;
Zebrafish;
Acute Lung Injury/drug therapy*
- From:
Journal of Southern Medical University
2025;45(5):1013-1022
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES: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.
CONCLUSIONS: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".
