2008 NSTI Nanotechnology Conference and Trade Show - Nanotech 2008 - 11th Annual

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TechConnect Summit
Clean Technology 2008

Dendrimeric Nanocontainers as Anti-Angiogenic Therapeutics

K.T. AL-Jamal, S. Akerman, J.E. Podesta, W.T. Al-Jamal, J.A. Turton, C. Kanthou, N. Vargesson, G.M. Tozer, K. Kostarelos
Nanomedicine Lab, UK

dendrimer, anti-angiogenic, window chamber, growth delay

Dendrimers are three-dimensional hyperbranched nanocontainers which have been experimentally investigated in cancer nanotechnology as tools for drug delivery to solid tumours, as contrast agents, and in cancer gene delivery via intratumoral and systemic administration. In this work, we examine cationic dendrimers as anti-angiogenics via systemic administration. Anti-angiogenic activity was tested in vitro by tubule formation assay. Dendrimer, at non-toxic concentrations, inhibited tubule formation by SVEC4-10 in a concentration dependent manner. Dendrimer has shown an antiangiogenic activity in ovo, producing avascuar zone in 20% and 100% of the eggs (4-days old embryo) at 25 and 50 µg/disc dose, respectively, after 24h incubation. In vivo activity of the dendrimer was tested by Matrigel plug assay, monitoring tumor vascularization of tumors implanted in the window chamber preparation, and finally by tumor growth delay studies. There was an inhibitory effect of dendrimer systemic administration (50mg/Kg) on b-FGF induced angiogenesis in the Matrigel plugs. By means of intravital microscopy, vasculature of treated tumors appeared to be thinner and sparser. Tumor growth delay experiment was conducted using C57Bl6 mice bearing subcutaneous B16F10 tumors, tumour growth was monitored daily up to 10 days. Once-daily tail vain administration on days 1 and 2 post-tumor implantation showed a growth delay which appeared to be significant on day 6. Cationic dendrimer showed antiangiogenic activity in vitro and in vivo, with a profound anti-tumour effect on xenografts.

Nanotech 2008 Conference Program Abstract