A novel cationic lipid with intrinsic antitumor activity to facilitate gene therapy of TRAIL DNA

被引：68
作者：
Luo, Cong [1 ,2 ,3 ]
Miao, Lei [1 ,2 ]
Zhao, Yi [1 ,2 ]
Musetti, Sara [1 ,2 ]
Wang, Yuhua [1 ,2 ]
Shi, Kai [1 ,2 ,3 ]
Huang, Leaf [1 ,2 ]
机构：
[1] Univ N Carolina, Eshelman Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Eshelman Sch Pharm, Ctr Nanotechnol Drug Delivery, Chapel Hill, NC 27599 USA
[3] Shenyang Pharmaceut Univ, Sch Pharm, Dept Pharmaceut, Shenyang 110016, Peoples R China
来源：
BIOMATERIALS | 2016年 / 102卷
关键词：
Cationic lipid; Metformin; Biguanide; Intrinsic antitumor activity; TRAIL; Nanoparticles; APOPTOSIS-INDUCING LIGAND; LUNG-CANCER CELLS; TARGETED DELIVERY; MAMMALIAN TARGET; TUMOR-GROWTH; AMPK; METFORMIN; KINASE; SENSITIZATION; SIRNA;
D O I：
10.1016/j.biomaterials.2016.06.030
中图分类号：
R318 [生物医学工程];
学科分类号：
0831 ;
摘要：
Metformin (dimethylbiguanide) has been found to be effective for the treatment of a wide range of cancer. Herein, a novel lipid (1,2-di-(9Z-octadecenoyl)-3-biguanide-propane (DOBP)) was elaborately designed by utilizing biguanide as the cationic head group. This novel cationic lipid was intended to act as a gene carrier with intrinsic antitumor activity. When compared with 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (DOTAP), a commercially available cationic lipid with a similar structure, the blank liposomes consisting of DOBP showed much more potent antitumor effects than DOTAP in human lung tumor xenografts, following an antitumor mechanism similar to metformin. Given its cationic head group, biguanide, DOBP could encapsulate TNF-related apoptosis-inducing ligand (TRAIL) plasmids into Lipid-Protamine-DNA (LPD) nanoparticles (NPs) for systemic gene delivery. DOBP-LPD-TRAIL NPs demonstrated distinct superiority in delaying tumor progression over DOTAP-LPD-TRAIL NPs, due to the intrinsic antitumor activity combined with TRAIL-induced apoptosis in the tumor. These results indicate that DOBP could be used as a versatile and promising cationic lipid for improving the therapeutic index of gene therapy in cancer treatment. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码：239 / 248
页数：10
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