Cationic lipid nanoparticles for therapeutic delivery of siRNA and miRNA to murine liver tumor.
Cationic lipid nanoparticles for therapeutic delivery of siRNA and miRNA to murine liver tumor.
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DOI：
10.1016/j.nano.2013.05.007
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发表时间：
2013-11
影响因子：
5.4
通讯作者：
Ghoshal, Kalpana
中科院分区：
文献类型：
--
作者：
Hsu, Shu-hao;Yu, Bo;Wang, Xinmei;Lu, Yuanzhi;Schmidt, Carl R.;Lee, Robert J.;Lee, L. James;Jacob, Samson T.;Ghoshal, Kalpana
MIR-122是一种肝脏特异的肿瘤抑制基因，在肝细胞癌中经常下调。LNP-DP1，一种阳离子脂质纳米制剂，被开发为一种载体，通过传递miR-122来恢复肝癌细胞中解除调控的基因表达。LNP-DP1由2-二烯氧基-N，N-二甲基-3-氨基丙烷(DODMA)、卵磷脂酰胆碱、胆固醇和胆固醇-聚乙二醇组分组成。在体外，LNP-DP1介导的miR-122模拟肝癌细胞的转染使miR-122靶基因下调95%。在小鼠肝癌模型中，包裹在LNP-DP1中的siRNAs/miRNAs在体内被肝细胞和肿瘤细胞优先摄取。在LNP-DP1中模拟的miR-122在肝癌细胞中具有功能，不会引起全身毒性。为了证明其治疗潜力，瘤内注射了包裹miR-122模拟分子的LNP-DP1，在30天内对肝癌移植瘤的生长抑制了~50%，这与靶基因抑制和血管生成障碍有很好的相关性。这些数据表明，LNP-DP1介导的microRNA传递作为一种新的肝癌治疗策略的潜力。
miR-122, a liver-specific tumor suppressor microRNA, is frequently downregulated 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 downregulated 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.
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影响因子：
56.9
作者：
Jopling, CL;Yi, MK;Sarnow, P
通讯作者：
Sarnow, P
聚乙二醇化免疫脂多聚复合物：一种用于肝癌治疗的新型非病毒基因递送系统
影响因子：
10.8
作者：
Hu, Yurong;Li, Kun;Zhang, Yun
通讯作者：
Zhang, Yun
影响因子：
64.8
作者：
Grimm, Dirk;Streetz, Konrad L.;Kay, Mark A.
通讯作者：
Kay, Mark A.
影响因子：
4
作者：
Kutay, Huban;Bai, Shoumei;Ghoshal, Kalpana
通讯作者：
Ghoshal, Kalpana
影响因子：
10.8
作者：
Geusens, B.;Lambert, J.;Van Gele, M.
通讯作者：
Van Gele, M.