Melone, Pietro
(2017)
Application of gH625 cell-penetrating peptide in advanced engineered materials.
[Tesi di dottorato]
Abstract
The hydrophobic nature of phospholipids membrane bilayer represent a selectively permeable barrier of living cells. In recent year, the use of cell-penetrating peptides (CPPs) in the delivery of various cargoes across cellular membranes has been widely explored. Among these, peptide gH625 was identified as a membrane-perturbing domain in the glycoprotein gH of Herpes simplex virus type I. gH625 is able to interacts with biological membranes, traverse them and carry a cargo into the cytoplasm. In this context, the aim of this work is to investigate the ability of the gH625 peptide in the construction of novel materials for therapeutic applications. Therefore, we firstly focused on the combined effects of gH625 peptide and reverse transfection in order to develop a gene delivery platform based on functionalized polyethylenimine (PEI)/DNA polyplexes. Then we analyzed the role of Pt NPs size in influencing the ability of gH625 to escape the endo-lysosomal pathway and deliver particles in the cytosol. Finally, we analyzed the behavior of gH625 in dual-functionalized polymeric carrier systems for targeted drug delivery across the blood-brain barrier.
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