The intriguing journey of gH625-dendrimers

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