Peptide based platforms for cancer drug delivery

Emiliana Perillo
2015
Cancer remains one of main causes of death in humans, accounting for 8.2 milion deaths worldwide in 2012. Chemotherapy, the most widely used cancer therapy, is the most effective and potent strategy to treat malignant tumors, but has the disadvantage of not delivering the therapeutic agents only to tumor sites. Nanomedicine may allow the controlled release of drugs by biodegradation and self-regulation of nanomaterials in vitro and in vivo. The goal of this PhD project was to create a delivery
more » ... ool, that transports the drug to the target cells not only with high efficacy, but also with minimal toxicity against normal cells and avoiding its degradation and entrapment in endosomes. The first part of this thesis was focused on the design of the strategies for the achievement of a toolbox easily to functionalize and on its obtainment. The second phase was the physico-chemical characterization of each selected nanosystem with particular attention to the size, zeta potential and drug loading and release. The third phase was to analyze in vitro the subcellular fate of the vectorized drug and the effect on the cells. Several nanosystems (liposomes, magnetic nanoparticles, polystyrene nanoparticles) were selected and functionalized with peptides both to enhance tumor targeting and facilitate intracellular uptake. In particular, we used a novel Cell Penetrating Peptide (namely, gH625) which is able to overcome the known limits of classic CPPs. In fact, gH625 is able to efficiently traverse biological membranes, promoting lipid-membrane reorganizing processes, such as fusion or pore formation and involving temporary membrane destabilization and subsequent reorganization; it is able to circumvent the endosomal entrapment either favouring the escape from the endosome or by directly translocating the drug across the membrane. In order to make the nanosystem cell and tissue specific, we have further functionalized the surface of the nanosystem with a targeting peptide. We exploited the EGB peptide, which recognizes the epiderm [...]
doi:10.6092/unina/fedoa/10162 fatcat:oduxbcky2jbcvfg3g274viaskm