The group is strongly dedicated to the development of delivery vehicles for in vitro and in vivo theranostics applications. The group has developed a new class of membranotropic peptides derived from viral glycoproteins involved in the entry process and can carry different types of cargos inside cells. The available Cell penetrating peptides transport their cargo inside cells essentially using endocytosis. The cargo needs to escape from the endosomal vesicle in order to exert its action. If the cargo remains entrapped in the endosomes, the degradation processes take place and abolish biological effects. On the contrary, membranotropic CPPs uptake mechanisms mainly involve direct penetration of the plasma membrane and, consequently, immediate bioavailability of the cargo. The prototype of these sequences is gH625. The group has reported the first use of membranotropic peptides for delivery across cell membranes and in particular for delivery across the Blood Brain Barrier.
One of the most important goals in cancer treatment is the achievement of pharmacologically active concentrations of chemotherapeutics in cancer tissues, avoiding drug distribution in healthy tissues. Up-to-date a plethora of pharmacological weapons are available in order to control cancer growth but for none of these selectivity toward cancer cells was demonstrated. Once accumulated in tumor tissues nanocarriers can release the drug or can be internalized in cancer cells through the endocytosis mechanism, resulting in intracellular trafficking in endosomes. Therefore, cleavage of the drugs out of nanocarriers and escape from the endosomes are further critical steps. Another complication of cancer therapy is the potential development of chemoresistance that is due to the selection of cancer cell clones expressing molecules that protect tumour cells from anti-cancer agents. The group has proposed the exploitation of the internalization properties of membranotropic peptides for vector-mediated internalization strategies. We showed the drug carrier ability of gH625 functionalized DOPG based liposomes encapsulating Doxo and revealed differences between the uptake mechanisms of free and encapsulated Doxo. Nuclear accumulation of free Doxo was attributed to drug diffusion, while encapsulated Doxo remained mostly in the cytoplasm with negligible nuclear accumulation. We recently reported on liposomes armed with gH625 that are able to overcome doxorubicin resistance in lung adenocarcinoma cell lines.