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

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. 1,2-Dioleoyl-3-trimethylammonium-propane LNPs were formulated, protein corona formed in nude mice serum and its impact on drug delivery were analyzed. 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. These results present an optimized LNP that selectively recruits endogenous proteins to its corona which may lead to enhanced delivery and transfection in tissues of interest.