کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5548161 | 1556465 | 2017 | 7 صفحه PDF | دانلود رایگان |
small interfering RNA (siRNA) has been suggested as a potential therapeutic molecule, whereby potent gene silencing is precisely controlled by RNAi machinery. Cationic liposome-protamine-DNA (LPD) has been traditionally used as the carrier of functional nucleic acids. The cytotoxicity derived from the cationic moiety has raised a concern to safely deliver nucleic acids, such as siRNA, to the target site. In the present study, LPD was coated with the natural anionic polymer, hyaluronic acid (HA), termed LPDH. The cytotoxicity and safety of LPDH was assessed in vitro. LPD induced hemolysis of murine red blood cells and cytotoxicity in human endothelial cells, while LPDH remarkably reduced the hemolysis and cytotoxicity when compared to LPD at the same concentration of siRNA. Fluorescently-labeled LPD showed increased cellular uptake when compared to LPDH. In contrast, LPD and LPDH showed similar effects on gene silencing for the luciferase gene on the luciferase-expressing B16F0 cancer cell line. PEGylated LPD obstructed this gene silencing effect. These results indicate that LPDH can reduce the cytotoxicity associated with LPD with a comparable gene silencing response, suggesting that the coating of hyaluronic acid with cationic carriers is effective strategy to deliver siRNA with less cytotoxicity.
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Journal: Journal of Drug Delivery Science and Technology - Volume 39, June 2017, Pages 435-441