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目的:应用NGR导向磷脂化合物修饰香豆素-6隐形脂质体以构建肿瘤新生血管靶向载体。方法:合成NGR导向磷脂化合物并进行了表征。采用薄膜法制备了不同比例NGR修饰的香豆素-6隐形脂质体,以包封率和泄漏率为指标,考察其稳定性;以人脐静脉血管内皮细胞(HUVEC,阳性细胞,CD13高表达)为靶细胞,用流式细胞仪和激光共聚焦显微镜对载体体外细胞摄取性质进行了分析。结果:制得的不同比例NGR修饰的香豆素-6隐形脂质体的包封率均>90.0%,12 h的体外累积泄漏率<9.0%。NGR修饰后的香豆素-6隐形脂质体在HUVEC中的摄取率明显高于未经修饰的隐形脂质体,且以0.64%(摩尔比)的用量摄取效果最好,而人冠状动脉内皮细胞(HCAEC,阴性细胞,CD13无表达)对两者的摄取没有明显差异。激光共聚焦观察表明,脂质体摄取入胞后,香豆素-6主要分布在细胞质中。结论:NGR修饰的隐形脂质体能够实现血管内皮细胞靶向,且用量以0.64%摩尔比为最佳。
OBJECTIVE: To use NGR-guided phospholipid compounds to modify coumarin-6 stealth liposomes to construct tumor neovascular targeting vector. Methods: NGR-directed phospholipid compounds were synthesized and characterized. Coumarin-6 stealth liposomes with different proportions of NGR were prepared by thin-film method. The encapsulation efficiency and leakage rate were used as indexes to investigate the stability of coumarin-6. HUVECs positive cells, CD13 Expression) as target cells, the use of flow cytometry and confocal laser scanning microscopy of the carrier in vitro cellular uptake properties were analyzed. Results: The entrapment efficiency of Coumarin-6 in different proportions of modified NGR was> 90.0%. The cumulative leakage rate in vitro was <9.0% after 12 hours. The uptake rate of NGR-modified coumarin-6 in liposomes in HUVEC was significantly higher than that of unmodified invisible liposomes, and the best effect was obtained at a dosage of 0.64% (molar ratio), whereas the human coronary artery There was no significant difference in uptake of both endothelial cells (HCAEC, negative cells, CD13 null). Confocal laser scanning showed that coumarin-6 mainly distributed in the cytoplasm after liposome uptake. CONCLUSION: NGR-modified stealth liposomes can target vascular endothelial cells and the optimal dosage is 0.64%.