A peptide derived from Herpes Simplex Virus type 1glycoprotein H: membrane translocation and applications to the delivery of quantum dots

Cell membranes are impermeable to most molecules not actively imported by living cells, including practically all macromolecules and even small molecules whose physiochemical properties prevent passive membrane diffusion. However, over the past decades, we have seen the development of increasingly sophisticated methodology for intracellular drug delivery. Cell-penetrating peptides (CPPs), representing different families of short peptides believed to enter cells by penetrating cell membranes, have attracted a great interest in the hope of enhancing gene therapy, vaccine development, and drug delivery. Nevertheless, to achieve an efficient intracellular delivery, further strategies to bypass the endocytotic pathway need to be investigated. We report on a novel peptide molecule derived from glycoprotein gH of Herpes simplex type I virus (gH625) which is able to traverse the membrane bilayer and to transport a cargo into the cytoplasm. In the present study, to accurately measure the fraction of internalised peptide, We also report confocal microscopy experiments showing the cellular uptake of gH625. In order to assess the ability of the peptide gH625 to deliver drugs inside the cell, we used quantum dots (QDs) as a model cargo. We showed that cargo molecule quantum dots, almost unable to traverse the membrane bilayer on their own, can gain constitutive access to the cell internal compartment and mainly by a non endocytotic route