Synthesis of cRGD-based bioconjugates as a tool for theranostic applications

In this PhD dissertation, the employment of a RGD-cyclopentapeptide (3a-RGD) as targeting agent in developing active targeting drug delivery systems to target tumour cells, that overexpress αVβ3 and αVβ5 on their surface, was discussed. Small molecule – drug conjugates (SMDC) were obtained exploiting a click reaction between the N3-3a-RGD and theranostic ethynyl-NDIs. The obtained SMDCs showed different internalization and toxicity profile with respect to the bare NDIs on glioblastoma cell lines. Silk fibroin-based nanoparticles were functionalized with 3a-RGD and employed as carrier of theranostic drugs towards bladder carcinoma and glioblastoma cells. DMPC-liposomes were decorated with 3a-RGD and the influence of the functionalization on the cellular uptake was assessed on cells of triple negative breast carcer. Furthermore, a new synthetic scheme that uses thiazol-5(4H)-ones as intermediates, for the obtainment of α-ethynyl quaternary amino acids endowed with easily cleavable N-protecting groups such as Cbz, has been achieved. These compounds may be employed in peptide synthesis for the attainment of variously functionalized peptides.