基于点击化学修饰的肿瘤靶向阿霉素脂质体的制备与表征

首先合成了叠氮化的胆固醇和炔基化的奥曲肽，并基于叠氮化的胆固醇制备了叠氮修饰的阿霉素脂质体Dox@N₃-L；随后利用点击反应在其表面修饰了具有肿瘤靶向功能的奥曲肽，得到奥曲肽靶向阿霉素脂质体Dox@Oct-L；最后考察了点击反应的进程、点击修饰对药物包封率的影响以及脂质体的体外靶向性。结果表明，通过点击反应能成功将奥曲肽修饰到载药载体表面，点击修饰对脂质体中荷载的药物没有影响，包封率为99.8%，与点击前无显著差异。细胞毒性实验结果显示，Dox@Oct-L对肿瘤细胞HepG2的杀伤作用强于Dox@N₃-L，表明Dox@Oct-L对HepG2细胞具有一定的靶向性。因此，利用点击化学在荷载药物的载体表面修饰是一种温和有效的方式，可方便地实现载药载体表面的功能化。

Preparation and characterization of tumor targeting doxorubicin liposomesmodified via click chemistry

In this study, octreotide targeting doxorubicin liposome(Dox@Oct-L)was prepared by modifying cholesterol with azide group to prepare azide-modified doxorubicin liposome(Dox@N₃-L), followed by click reaction on the vehicle surface with alkyne-modified octreotide. HPLC chromatographic determination showed that octreotide was successfully attached to drug loaded liposome. No significant effect of click modification on the drug loaded within liposome was detected, and the entrapment efficiency of Dox@Oct-L was 99. 8%. Dox@Oct-L showed improved in vitro anti-tumor activity against HepG2 cell when compared with Dox@N₃-L, demonstrating that Dox@Oct-L possessed targeting ability against HepG2 cell. Therefore, the click chemistry in modification of drug-loading carrier surface is gentle and efficient, providing the possibility to functional modification in drug-loading carrier surface convieniently.