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 125I 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 IC(50) (0.015 muM) than pure Ara-C and in vivo an oncostatic index higher than 160%.
Jasseron
S
S
Laboratoire de chimie bioorganique et des systèmes moléculaires vectoriels, Université d'Avignon, 33, rue Louis Pasteur, 84000, Avignon, France.
Contino-Pépin
C
C
Maurizis
J C
JC
Rapp
M
M
Pucci
B
B
D000179:Acrylates / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003561:Cytarabine / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D008297:Male; D008744:Methylamines / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D009842:Oligopeptides / Q000737:chemistry* / Q000493:pharmacokinetics; D011355:Prodrugs / Q000378:metabolism; D014018:Tissue Distribution
D000179:Acrylates; D004337:Drug Carriers; D008744:Methylamines; D009842:Oligopeptides; D011355:Prodrugs; D003561:Cytarabine; C053576:N-acryloyl-tris(hydroxymethyl)aminomethane; C047981:arginyl-glycyl-aspartic acid