Poster abstracts

Poster number 64 submitted by Shu-hao Hsu

Cationic lipid based nanoparticles for therapeutic delivery of miRNA-122 to mouse liver tumors

Shu-hao Hsu (Molecular, Cellular, and Developmental Biology Program), Bo Yu, Xinmei Wang (NSF Nanoscale Science and Engineering Center NSEC), Robert J. Lee (Division of Pharmaceutics, College of Pharmacy; NSF Nanoscale Science and Engineering Center NSEC), L. James Lee (Department of Chemical and Biomolecular Engineering; NSF Nanoscale Science and Engineering Center NSEC), Samson T. Jacob (Department of Molecular and Cellular Biochemistry; Comprehensive Cancer Center), Kalpana Ghoshal (Department of Pathology; Comprehensive Cancer Center)

Abstract:
To restore dysregulated gene expression resulting from loss of microRNA, lipid nanoparticles (LNPs) were developed as vehicles for systemic delivery (1-2). The novel LNPs, termed LNP-DP1, consist of a conditionally ionizable cationic lipid, 2-dioleyloxy-N,N-dimethyl-3-aminopropane (DODMA), egg PC, cholesterol (Chol) and Chol-polyethylene glycol (Chol-PEG). miR-122 is the most abundant liver-specific tumor suppressor microRNA (3-4), which is downregulated in primary HCC (5-6). Transfection of miR-122 to HCC cell lines by LNP-DP1 diminished expression of miR-122 targets by >95%. LNP-DP1 was preferentially taken up by hepatocytes and tumor epithelial cells as demonstrated by systemic delivery of fluorescence labeled siRNA by LNP-DP1 in different mouse models of HCC. LNP-DP1 did not induce significant liver or kidney damage in mice. miR-122 was successfully delivered and found to be functional in hepatocytes and tumor cells as demonstrated by downregulation of several target genes. To demonstrate therapeutic potential of miR-122, LNP-DP1 encapsulating miR-122 was intratumorally injected into HCC xenograft developed in nude mice. The tumor mass was reduced by nearly 50% within 30 days after delivery of miR-122, which correlated well with reduced expression of its target genes and proliferation marker. These data demonstrate the potential of LNP mediated microRNA delivery as an alternate strategy for HCC therapy.

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Keywords: miR-122, nanoparticle, HCC