Lactosylated gramicidin-based lipid nanoparticles (Lac-GLN) for targeted delivery of anti-miR-155 to hepatocellular carcinoma.
Lactosylated gramicidin-based lipid nanoparticles (Lac-GLN) for targeted delivery of anti-miR-155 to hepatocellular carcinoma.
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DOI：
10.1016/j.jconrel.2013.03.020
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发表时间：
2013-06-28
期刊：
影响因子：
--
通讯作者：
Lee RJ
中科院分区：
文献类型：
--
作者：
Zhang M;Zhou X;Wang B;Yung BC;Lee LJ;Ghoshal K;Lee RJ
制备了乳糖化革兰西丁脂质纳米粒(Lac-Gln)，用于将抗microRNA-155(抗miR-155)输送到肝细胞癌(HCC)细胞。MIR-155是一种癌基因，在肝细胞癌中经常升高。该纳米粒的平均粒径为73 nm，zeta电位为+3.5mV，包封率为88%，在4°C下具有良好的胶体稳定性，可有效地为肝癌细胞提供抗miR-155，靶向C/eBPβ和XFOP3基因的上调分别为16.1倍和4.1倍，并表现出比Lipofetamine2000更高的效率。在小鼠体内，静脉注射含有Cy3-抗miR-155的Lac-Gln可导致抗miR-155在肝细胞中优先积聚。静脉注射1.5 mg/kg抗miR-155Lac-Gln可使C/EBPβ和FOXP3表达分别上调6.9倍和2.2倍。这些结果提示了Lac-Gln作为肝脏特异性载体用于抗miR治疗的潜在应用。
Lactosylated gramicidin-containing lipid nanoparticles (Lac-GLN) were developed for delivery of anti-microRNA-155 (anti-miR-155) to hepatocellular carcinoma (HCC) cells. MiR-155 is an oncomiR frequently elevated in HCC. The Lac-GLN formulation contained N-lactobionyl-dioleoyl phosphatidylethanolamine (Lac-DOPE), a ligand for the asialoglycoprotein receptor (ASGR), and an antibiotic peptide gramicidin A. The nanoparticles exhibited a mean particle diameter of 73 nm, zeta potential of +3.5 mV, anti-miR encapsulation efficiency of 88%, and excellent colloidal stability at 4°C. Lac-GLN effectively delivered anti-miR-155 to HCC cells with a 16.1- and 4.1-fold up-regulation of miR-155 targets C/EBPβ and FOXP3 genes, respectively, and exhibited significant greater efficiency over Lipofectamine 2000. In mice, intravenous injection of Lac-GLN containing Cy3-anti-miR-155 led to preferential accumulation of the anti-miR-155 in hepatocytes. Intravenous administration of 1.5 mg/kg anti-miR-155 loaded Lac-GLN resulted in up-regulation of C/EBPβ and FOXP3 by 6.9- and 2.2- fold, respectively. These results suggest potential application of Lac-GLN as a liver-specific delivery vehicle for anti-miR therapy.
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