High‐Density Lipoprotein Nanoparticles Deliver RNAi to Endothelial Cells to Inhibit Angiogenesis
Year: 2014
Type: article
Abstract: Systemic delivery of therapeutic nucleic acids to target cells and tissues outside of the liver remains a major challenge. A biomimetic high‐density lipoprotein nanoparticle (HDL NP) is synthesized for delivery of a cholesteryl‐modified therapeutic nucleic acid to vascular endothelial cells (ECs), a cell type naturally targeted by HDL. HDL NPs adsorb cholesteryl‐modified oligonucleotides and protect them from nuclease degradation. As proof of principle, we deliver RNAi targeting vascular endothelial growth factor receptor 2 (VEGFR2) to ECs to effectively silence target mRNA and protein expression in vitro. In addition, data show that treatment strongly attenuates in vivo neovascularization measured using a standard angiogenesis assay and in hypervascular tumor allografts where a striking reduction in tumor growth is observed. For effective delivery, HDL NPs require the expression of the cell surface protein scavenger receptor type‐B1 (SR‐B1). No toxicity of HDL NPs is measured in vitro or after in vivo administration. Thus, by using a biomimetic approach to nucleic acid delivery, data demonstrate that systemically administered RNAi–HDL NPs target SR‐B1 expressing ECs to deliver functional anti‐angiogenic RNAi as a potential treatment of cancer and other neovascular diseases.
Authors: Sushant Tripathy, Elena Vinokour, Kaylin M. McMahon, Olga V. Volpert, C. Shad Thaxton
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Apigenin restores TSP-1 expression in UVB-irradiated keratinocytes, High Density Lipoprotein Nanoparticles for siRNA Delivery, Novel Antiangiogenic Peptides for Treatment of Exudative AMD, Nanomaterials for Cancer Diagnostics and Therapeutics, The Robert H. Lurie Comprehensive Cancer Center, Carcinogenesis Training Program
OpenAlex ID: W2055457307