文献：ICAM-1-Targeted Liposomes Loaded with Liver X Receptor Agonists Suppress PDGFInduced Proliferation of Vascular Smooth Muscle Cells

文献链接：https://pubmed.ncbi.nlm.nih.gov/28472871/

作者：Xu Huang1 , Meng-Qi Xu1, Wei Zhang , Sai Ma , Weisheng Guo, Yabin Wang, Yan Zhang , Tiantian Gou , Yundai Chen , Xing-Jie Liang and Feng Cao

相关产品：DSPE-PEG-mal

原文摘要：The proliferation of vascular smooth muscle cells (VSMCs) is one of the key events during the progress of atherosclerosis. The activated liver X receptor (LXR) signalling pathway is demonstrated to inhibit platelet-derived growth factor BB (PDGF-BB)-induced VSMC proliferation. Notably, following PDGF-BB stimulation, the expression of intercellular adhesion molecule-1 (ICAM-1) by VSMCs increases significantly. In this study, anti-ICAM-1 antibodyconjugated liposomes were fabricated for targeted delivery of a water-insoluble LXR agonist (T0901317) to inhibit VSMC proliferation. The liposomes were prepared by filming-rehydration method with uniform size distribution and considerable drug entrapment efficiency. The targeting effect of the anti-ICAM-T0901317 liposomes was evaluated by confocal laser scanning microscope (CLSM) and flow cytometry. Anti-ICAM-T0901317 liposomes showed significantly higher inhibition effect of VSMC proliferation than free T0901317 by CCk8 proliferation assays and BrdU staining. Western blot assay further confirmed that anti-ICAM-T0901317 liposomes inhibited retinoblastoma (Rb) phosphorylation and MCM6 expression. In conclusion, this study identified anti-ICAM-T0901317 liposomes as a promising nanotherapeutic approach to overcome VSMC proliferation during atherosclerosis progression.

DSPE-PEG-mal中的PEG链能够增加脂质体的亲水性，提高脂质体在水溶液中的稳定性。同时，PEG链还能够减少脂质体与血浆蛋白的非特异性结合，降低脂质体被清除的速率，延长其在体内的循环时间。在T0901317和香豆素-6的装载过程中，DSPE-PEG-mal作为连接桥梁，将药物分子与脂质体连接起来，提高药物的靶向性和递送效率。

图为：膜-复水法制备抗icam-1-t0901317脂质体

DSPE-PEG-mal在T0901317和香豆素-6装载脂质体制备中的作用：

采用膜复水法制备treat性荧光脂质体。简单地说，将PC、Chol、DSPE-PEG2000和DSPE-PEG-mal组合在含有氯仿/甲醇的圆底瓶中，两种不同的重量比T0901317。该混合物在室温下用旋转蒸发器干燥，形成薄膜。然后在真空泵中处理薄膜，在的PBS中水合，并在下超声几分钟。为了优化脂质体的形成，对混合物的组成进行评估。T0901317的重量比影响了封装百分率和加载效率。通过过滤去除未溶解的T0901317。

图为：抗icam-1-T0901317脂质体使细胞停留在G1中

结论：DSPE-PEG-ma的使用是因为它有许多优势，包括靶向诊断和Treatment 、缓释药物释放和合适的疏水性。T0901317通过阻止Rb的磷酸化来调节vsmc中的脂质积累，并抑制平滑肌细胞的增殖。经PDGF-BB处理后高表达的ICAM-1被选为含有T0901317的缓释脂质体的靶点。目的是抑制平滑肌细胞增殖。