Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1425569 | Journal of Controlled Release | 2010 | 9 Pages |
Abstract
Hypoxia is a strong modulator of angiogenesis, accelerating adipose tissue expansion, suggesting that hypoxia inducible factor 1α (HIF1α) can be a novel target for anti-obesity. We conjugated antisense-HIF1α-oligonucleotide (ASO) with low molecular weight protamine (LMWP), a cell-penetrating peptide, to enhance its ability to block hypoxic-angiogenesis, thereby eliciting an anti-obesity effect. Nano-sized ASO-LMWP (AS-L) conjugates enhanced cellular uptake of ASO without yielding a cytotoxic effect and protected the ASO against enzymatic attack and chemical reduction. AS-L showed enhanced intra-cellular localization compared to naked ASO and the complex of ASO with lipofectamine during hypoxic-differentiation. Consequently AS-L induced significant down-regulation of leptin and VEGF gene expressions, thereby reducing fat accumulation in the cell.This proof-of-concept study shows that AS-L produces an inhibitory effect on adipogenesis and angiogenesis during differentiation, indicating LMWP mediated ASO delivery can potentially be a safe and promising treatment for obesity.
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Physical Sciences and Engineering
Materials Science
Biomaterials
Authors
Yoon Shin Park, Yongzhuo Huang, Yoon Jeong Park, Allan E. David, Lindsay White, Huining He, Hee Sun Chung, Victor C. Yang,