High-Density lipoprotein nanoparticles deliver RNAi to endothelial cells to inhibit angiogenesis

Sushant Tripathy, Elena Vinokour, Kaylin M. McMahon, Olga V. Volpert*, C. Shad Thaxton

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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 cholesterylmodified therapeutic nucleic acid to vascular endothelial cells (ECs), a cell type naturally targeted by HDL. HDL NPs adsorb cholesteryl-modifi ed 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.

Original languageEnglish (US)
Pages (from-to)1141-1150
Number of pages10
JournalParticle and Particle Systems Characterization
Volume31
Issue number11
DOIs
StatePublished - Nov 1 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics

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