Abstract EN:

Nowadays, it is well known that the angiogenesis or neovascularization phenomenon participates greatly to the tumour growth. A transmembrane protein, the integrin avb3, is over-expressed on the outer surface of the angiogenic cells. This membrane protein admits, as specific ligand, a short peptide, the RGD sequence. According to these observations, the work presented herein deals with the synthesis, the physico chemical and the biological studies of molecular or macromolecular carriers, endowed with the RGD sequence, able to target the tumour angiogenesis sites. Grafting RGD sequences onto telomers, a kind of short macromolecular carriers derived from THAM, allowed us to show an accumulation of these molecules within the tumour stroma. Furthermore, by endowing these macromolecules with an antimitotic agent such as Ara-C, the measurements of their cytotoxicity towards B16 melanoma cells line and their oncostatic index determination on mice carrying B16 melanoma, fully showed the validity of this targeting concept. In other respects, similar studies were carried out with amphiphilic molecular compounds equipped with a fluorinated chain as hydrophobic part and a RGD sequence as polar head. The biodistribution assays have confirmed the potentialities of these amphiphilic carriers including RGD sequences to target the neovascularization sites. However, according to the hydrophilic or lipophilic property of the chosen drug, the final structure of the molecular carrier has to be shaped in order to provide the best bioavailability to the prodrug. The cytotoxicity and the oncostatic index of this kind of amphiphilic carriers bearing an Ara-C moiety have been specified on mice carrying B16 melanoma, too. These assays have clearly shown the interest of such a vectorization concept