title: Polyethylenimine modified liposomes as potential carriers for antitumor drug delivery in vitro.
abstract: 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.
authors: Department of Pharmacy, Zhejiang University City College, Hangzhou, Zhejiang, PR China.
authors: Xiaoyi
authors: X
authors: Sun
authors: Jinliang
authors: J
authors: Chen
authors: Hailiang
authors: H
authors: Chen
authors: Wenquan
authors: W
authors: Liang
mesh_terms: D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival; D002945:Cisplatin / Q000008:administration & dosage; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D010316:Particle Size; D010984:Platinum / Q000737:chemistry / Q000378:metabolism; D011094:Polyethyleneimine / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D002412:Cations; D004337:Drug Carriers; D008081:Liposomes; D010984:Platinum; D011094:Polyethyleneimine; D002945:Cisplatin