Role of vitronectin-rich protein corona on tumor-specific siRNA delivery and transfection with lipid nanoparticles

Nanomedicine (Lond). 2021 Mar;16(7):535-551. doi: 10.2217/nnm-2020-0428. Epub 2021 Mar 8.

Abstract

Aim: To evaluate the role of vitronectin-enriched protein corona on systemic delivery of siRNA-encapsulated cationic lipid nanoparticles (LNPs) to αvβ3 integrin expressing solid tumors. Materials & methods: 1,2-Dioleoyl-3-trimethylammonium-propane LNPs were formulated, protein corona formed in nude mice serum and its impact on drug delivery were analyzed. Results: 1,2-Dioleoyl-3-trimethylammonium-propane-containing LNP led to enhanced recruitment of vitronectin and showed preferential transfection to αvβ3-expressed cells relative to controls. Upon systemic administration in mice, the LNPs accumulated in the αvβ3-expressing endothelial lining of the tumor blood vessels before reaching tumor cells. Conclusion: These results present an optimized LNP that selectively recruits endogenous proteins in situ to its corona which may lead to enhanced delivery and transfection in tissues of interest.

Keywords: endogenous targeted delivery; in vitro and in vivo; lipid nanoparticle; protein corona; vitronectin; αvβ3 integrins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Lipids
  • Mice
  • Mice, Nude
  • Nanoparticles*
  • Protein Corona
  • RNA, Small Interfering / genetics
  • Transfection
  • Vitronectin

Substances

  • Lipids
  • Protein Corona
  • RNA, Small Interfering
  • Vitronectin