Lipid–peptide bioconjugation through pyridyl disulfide reaction chemistry and its application in cell targeting and drug delivery

Abstract

Background: The design of efcient drug delivery vectors requires versatile formulations able to simultaneously direct a multitude of molecular targets and to bypass the endosomal recycling pathway of cells. Liposomal-based vectors need the decoration of the lipid surface with specifc peptides to fulfll the functional requirements. The unspecifc binding of peptides to the lipid surface is often accompanied with uncontrolled formulations and thus preventing the molecular mechanisms of a successful therapy.

Results: We present a simple synthesis pathway to anchor cysteine-terminal peptides to thiol-reactive lipids for ade quate and quantitative liposomal formulations. As a proof of concept, we have synthesized two diferent lipopeptides based on (a) the truncated Fibroblast Growth Factor (tbFGF) for cell targeting and (b) the pH sensitive and fusogenic GALA peptide for endosomal scape.

Conclusions: The incorporation of these two lipopeptides in the liposomal formulation improves the fbroblast cell targeting and promotes the direct delivery of cargo molecules to the cytoplasm of the cell. Keywords: Smart liposomes, Disulfde bonds, Targeting peptide, GALA, Endosomal escape.