Enhanced Uptake and Endosomal Release of LbL Microcarriers Functionalized with Reversible Fusion Proteins

ACS Appl Bio Mater. 2020 Mar 16;3(3):1553-1567. doi: 10.1021/acsabm.9b01168. Epub 2020 Feb 18.


The efficient application of smart drug-delivery systems requires further improvement of their cellular uptake and in particular their release from endolysosomal compartments into the cytoplasm of target cells. The usage of virus proteins allows for such developments, as viruses have evolved efficient entry mechanisms into the cell, mediated by their fusion proteins. In our investigations, the transferability of the glycoprotein G which is a fusion protein of the vesicular stomatitis virus (VSV-G) onto the surface of a layer-by-layer (LbL) designed microcarrier was investigated. The assembly of VSV-G as a reversible viral fusion protein onto LbL microcarriers indeed induced an enhanced uptake rate on Vero cells as well as a fast and efficient release of the intact carriers from endolysosomes into the cytoplasm. Additionally, neither virus-associated effects on cellular viability nor activation of an interferon response were detected. Our study emphasizes the suitability of VSV-G as an efficient surface functionalization of drug-delivery systems.

Keywords: Rab5; bafilomycin; drug-delivery system; dynasore; endolysosomal release; supported lipid layer; uptake; virus proteins.