In vitro and in vivo evaluations of THAM derived telomers bearing RGD and Ara-C for tumour neovasculature targeting

As an approach to the development of specific drug delivery systems, a new class of low macromolecular carriers called 'telomers' endowed with an antitumour agent, such as arabinofuranosylcytosine (Ara-C), RGDSK peptidic sequences, as tumour targeting moieties, and tyrosine groups labelled with I-125 atoms allowing the in vivo scintigraphic follow up, were synthesized. Their tumour targeting ability was assessed in vivo in mice bearing a murine B16 melanoma. The biological results showed that the presence of RGDSK sequences onto the macromolecules leads to the selective targeting and the accumulation of telomers within the vascularized zone of the tumour. Moreover, such compounds exhibited in vitro a better IC50 (0.015 muM) than pure Ara-C and in vivo an oncostatic index higher than 160%. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.