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Journal Article
Research Support, N.I.H., Extramural
A novel cationic lipid with intrinsic antitumor activity to facilitate gene therapy of TRAIL DNA.
Biomaterials 2016 September
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.
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