NANOMEDICINE-UK. 2021; 16, 7: 535-551 DOI:10.2217/nnm-2020-0428

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

Chen, DY; Ganesh, S; Wang, WM; Lupieri, A; Amiji, M

Abstract

Aim: To evaluate the role of vitronectin-enriched protein corona on systemic delivery of siRNA-encapsulated cationic lipid nanoparticles (LNPs) to alpha v beta 3 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 alpha v beta 3-expressed cells relative to controls. Upon systemic administration in mice, the LNPs accumulated in the alpha v beta 3-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.

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Lipids

siRNA delivery and transfection using lipid nanoparticles (LNPs) is a cutting-edge approach for gene silencing in therapeutic applications. LNPs are engineered to encapsulate siRNA, protecting it from enzymatic degradation and ensuring stability during circulation. Their lipid bilayer structure, often enhanced with cationic or ionizable lipids, facilitates efficient cellular uptake and endosomal escape, enabling the siRNA to reach its target mRNA within the cell. This method is highly efficient in silencing specific genes, making it a powerful tool for treating genetic disorders, cancers, and viral infections. The versatility of lipid nanoparticles in targeting diverse cell types and tissues makes them a promising delivery system in the development of siRNA-based therapies.

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