[Design and inflammation-targeting efficiency assessment of an engineered liposome-based nanomedicine delivery system targeting E-selectin].

Q3 Medicine
Yumeng Ye, Bo Yu, Shasha Lu, Yu Zhou, Meihong Ding, Guilin Cheng
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引用次数: 0

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".

[一种以e-选择素为靶点的工程脂质体纳米药物递送系统的设计和炎症靶向效率评估]。
目的:开发一种靶向e -选择素的纳米药物递送系统,该系统可竞争性地抑制e -选择素与中性粒细胞配体的结合,从而阻断中性粒细胞粘附血管并抑制其向病变部位的募集。方法:采用插入后法,制备载盐酸阿霉素(DOX)脂质体(IEL-Lip/DOX)与e -选择素亲和肽IELLQARC偶联。两种配方[2-1P: Mol(PC): Mol(DPI)=100:1;制备了2-3P: 100:3],并测定了其修饰密度和体外释放特性。通过lps诱导炎症细胞模型、小鼠急性肺损伤(ALI)模型、大鼠股动脉物理损伤性炎症模型和斑马鱼局部炎症模型评估其靶向作用。结果:制备的IEL-Lip/DOX 2-1P和2-3P的肽修饰密度分别为4.76和7.57 pmoL/cm2。与未修饰的脂质体相比,IEL-Lip/DOX在pH 5.5时48小时累积释放率显著降低。在炎症细胞模型中,il - lip /DOX被激活的炎症内皮细胞摄取增加,2-1P表现出更高的跨内皮能力。在ALI小鼠肺组织中,IEL-Lip/Cy5.5的荧光强度较正常小鼠肺组织增加53.71% [Z-(2-1P)]和93.41% [Z-(2-3P)], 2-1P在炎性肺组织中的分布较正常小鼠肺组织增加24.19%。在大鼠股动脉模型中,2-1P具有更大的损伤血管/正常血管荧光强度对比。在斑马鱼模型中,2-1P和2-3P在炎症部位都显示出增加的聚集。结论:该e -selectin靶向纳米药物递送系统有效靶向活化的炎症内皮细胞,提高炎症部位的药物浓度,为治疗中性粒细胞介导的炎症性疾病提供了新的策略,实践了“一药多病”的理念。
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来源期刊
南方医科大学学报杂志
南方医科大学学报杂志 Medicine-Medicine (all)
CiteScore
1.50
自引率
0.00%
发文量
208
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