The intriguing journey of gH625-dendrimers

Abstract

The knowledge of the mechanism used by vectors to gain access to cell interiors is key to the development\ud of effective drug delivery tools for different pathologies. The role of the initial interaction with the\ud membrane bilayer is widely recognized, although not fully understood. We use neutron reflectivity\ud experiments and internalization studies with cells to reveal the extent of interaction of dendrimers\ud functionalized with the peptide gH625 with biomimetic membranes. We further investigate the\ud internalization by use of Caco-2 cells for assessing the membrane permeability properties of the\ud peptide–dendrimer construct. Neutron reflectivity allowed for the hypothesis that the peptide–\ud dendrimer is able to pass across the bilayer which was confirmed via permeability studies. We find that\ud gH625-dendrimers interact more strongly with cholesterol containing membranes. The advances in our\ud understanding of the mechanism of drug uptake are extremely useful to push further the design of new\ud drug delivery systems

Dimerization in tailoring uptake efficacy of the HSV-1 derived membranotropic peptide gH625

“…We have previously demonstrated a strong correlation between the affinity of gH625 for the lipid bilayer and cellular delivery efficiency, which is consistent with its uptake by a physically mediated process 23 – 26 ; in fact, to fully describe the biophysical mechanism involved in the molecular mode of action of gH625, the contribution of electrostatic and hydrophobic forces to the process is an essential piece of the puzzle that needs to be elucidated 7 .…”

Dendrimers: Amazing Platforms for Bioactive Molecule Delivery Systems

“…The dendrimers, as we have said before, constitute a class of nanoparticles with physicochemical characteristics that make them very attractive in nanomedicine applications, more specifically as drug delivery systems (DDS). As previously mentioned, these extraordinary dendritic macromolecules have an improved membrane permeability and tumor retention effects [87][88][89], due to their suitable structural properties and size control.…”

Versatility of cell-penetrating peptides for intracellular delivery of siRNA

“…The hydrophobicity and amphipathicity are the key features of gH625 that make the peptide interact with membrane lipids and form a transient helical structure to induce membrane organization temporarily. Thereby, it was demonstrated that gH625 is able to cross the cell membrane and to transport many conjugated cargoes into the cytosol (Falanga, Lombardi, et al., 2017; Falanga, Valiante, et al., 2017; Falanga, Galdiero et al., 2018).…”