Sun Xiaoyi, Chen Jinliang, Chen Hailiang, Liang Wenquan
Department of Pharmacy, Zhejiang University City College, Hangzhou, Zhejiang, PR China.
Pharmazie. 2012 May;67(5):426-31.
The transfection agent polycation polyethylenimine (PEI) has been rarely used to construct liposomes for chemical antitumor drugs. In this study, it was introduced into cisplatin (CDDP) encapsulated neutral liposomes (CDDP-NL) by amphiphilic PEI-cholesterol (PEI-Chol) to investigate its effect on the antitumor activity in A549 cells. The IC50 was 0.65 +/- 0.02, 2.94 +/- 0.21 and 2.03 +/- 0.15 microg/ml for CDDP-cationic liposomes (CDDP-CL), CDDP-NL and free CDDP, respectively. The enhanced anticancer activity was attributed to the addition of PEI-Chol which influenced cellular processing of CDDP. With the help of inhibitors, we found that besides clathrin dependent and actin dependent uptake pathways, caveolae-mediated endocytosis was involved in the internalization of CDDP-CL. Improved internalization of CDDP was observed. Intracellular Pt accumulations were 6.5 times and 3 times of those in CDDP-NL and free CDDP groups, respectively. The differences of intracellular location caused by endocytosis routes and lysosomes escape capacity of PEL-Chol was observed by fluorescence colocalization studies. PEI-Chol also decreased the Pt fraction exported out of cells and extended the cellular Pt retention of CDDP liposomes. In conclusion, cationic modification of liposomes with PEI is a potential and promising way for antitumor drug delivery.
转染剂聚阳离子聚乙烯亚胺（PEI）很少用于构建化学抗肿瘤药物的脂质体。在本研究中，通过两亲性PEI-胆固醇（PEI-Chol）将其引入顺铂（CDDP）包封的中性脂质体（CDDP-NL）中，以研究其对A549细胞抗肿瘤活性的影响。CDDP阳离子脂质体（CDDP-CL）、CDDP-NL和游离CDDP的IC50分别为0.65±0.02、2.94±0.21和2.03±0.15μg/ml。抗癌活性的增强归因于PEI-Chol的添加，其影响了CDDP的细胞处理过程。借助抑制剂，我们发现除了网格蛋白依赖性和肌动蛋白依赖性摄取途径外，小窝介导的内吞作用也参与了CDDP-CL的内化。观察到CDDP的内化有所改善。细胞内铂的积累分别是CDDP-NL组和游离CDDP组的6.5倍和3倍。通过荧光共定位研究观察到内吞途径和PEL-Chol的溶酶体逃逸能力导致的细胞内定位差异。PEI-Chol还降低了细胞排出的铂分数，并延长了CDDP脂质体在细胞内的铂保留时间。总之，用PEI对脂质体进行阳离子修饰是一种潜在且有前景的抗肿瘤药物递送方式。
