کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
877442 911026 2013 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cationic lipid nanoparticles for therapeutic delivery of siRNA and miRNA to murine liver tumor
موضوعات مرتبط
مهندسی و علوم پایه سایر رشته های مهندسی مهندسی پزشکی
پیش نمایش صفحه اول مقاله
Cationic lipid nanoparticles for therapeutic delivery of siRNA and miRNA to murine liver tumor
چکیده انگلیسی

miR-122, a liver-specific tumor suppressor microRNA, is frequently down-regulated in hepatocellular carcinoma (HCC). LNP-DP1, a cationic lipid nanoparticle formulation, was developed as a vehicle to restore deregulated gene expression in HCC cells by miR-122 delivery. LNP-DP1 consists of 2-dioleyloxy-N,N-dimethyl-3-aminopropane (DODMA), egg phosphatidylcholine, cholesterol and cholesterol-polyethylene glycol. In vitro, LNP-DP1-mediated transfection of a miR-122 mimic to HCC cells down-regulated miR-122 target genes by > 95%. In vivo, siRNAs/miRNAs encapsulated in LNP-DP1 were preferentially taken up by hepatocytes and tumor cells in a mouse HCC model. The miR-122 mimic in LNP-DP1 was functional in HCC cells without causing systemic toxicity. To demonstrate its therapeutic potential, LNP-DP1 encapsulating miR-122 mimic was intratumorally injected and resulted in ~ 50% growth suppression of HCC xenografts within 30 days, which correlated well with suppression of target genes and impairment of angiogenesis. These data demonstrate the potential of LNP-DP1-mediated microRNA delivery as a novel strategy for HCC therapy.From the Clinical EditorIn this study, LNP-DP1 –a cationic lipid nanoparticle formulation –is reported as a vehicle to restore deregulated gene expression in hepatic carcinoma cells by siRNA and miRNA delivery using a mouse model. Further expansions to this study may enable transition to clinical trials of this system.

Graphical AbstractThe schematic representation of mi-/si-RNA encapsulated by PEG modified LNP-DP1 which is mainly composed of EggPC, cholesterol and cationic lipid DODMA. The LNP-DP1 (red particles) can be specifically and efficiently taken up by hepatocytes and tumor cells (blue nuclei and green cell outline) after delivery to liver through mouse tail vein injection (Main text Figure 1B and 3C)Figure optionsDownload high-quality image (166 K)Download as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Nanomedicine: Nanotechnology, Biology and Medicine - Volume 9, Issue 8, November 2013, Pages 1169–1180
نویسندگان
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