TY - JOUR
T1 - Lactosylated gramicidin-based lipid nanoparticles (Lac-GLN) for targeted delivery of anti-miR-155 to hepatocellular carcinoma
AU - Zhang, Mengzi
AU - Zhou, Xiaoju
AU - Wang, Bo
AU - Yung, Bryant C.
AU - Lee, Ly J.
AU - Ghoshal, Kalpana
AU - Lee, Robert J.
N1 - Funding Information:
This work was supported by the grants DK088076 (K.G) and CA152969 (K.G., S.T.J., L.J.L. and R.L.) from National Institutes of Health . The authors wish to thank Richard Montione from OSU CMIF for the help on TEM imaging.
PY - 2013/5/9
Y1 - 2013/5/9
N2 - 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.
AB - 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.
KW - Asialoglycoprotein receptor
KW - Drug targeting
KW - Gramicidin
KW - Hepatocellular carcinoma
KW - Nanoparticles
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U2 - 10.1016/j.jconrel.2013.03.020
DO - 10.1016/j.jconrel.2013.03.020
M3 - Article
C2 - 23567045
AN - SCOPUS:84877058809
VL - 168
SP - 251
EP - 261
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 3
ER -