1. J Control Release. 2009 Dec 3;140(2):166-73. Epub 2009 Aug 20.

Targeting of tumor endothelium by RGD-grafted PLGA-nanoparticles loaded with
Paclitaxel.

Danhier F, Vroman B, Lecouturier N, Crokart N, Pourcelle V, Freichels H, Jérôme
C, Marchand-Brynaert J, Feron O, Préat V.

Université Catholique de Louvain, Unité de Pharmacie Galénique, Avenue Mounier
73-20, 1200 Brussels, Belgium.

Paclitaxel (PTX)-loaded PEGylated PLGA-based nanoparticles (NP) have been
previously described as more effective in vitro and in vivo than Taxol. The aim
of this study was to test the hypothesis that our PEGylated PLGA-based
nanoparticles grafted with the RGD peptide or RGD-peptidomimetic (RGDp) would
target the tumor endothelium and would further enhance the anti-tumor efficacy of
PTX. The ligands were grafted on the PEG chain of PCL-b-PEG included in the
nanoparticles. We observed in vitro that RGD-grafted nanoparticles were more
associated to Human Umbilical Vein Endothelial cells (HUVEC) by binding to
alpha(v)beta(3) integrin than non-targeted nanoparticles. Doxorubicin was also
used to confirm the findings observed for PTX. In vivo, we demonstrated the
targeting of RGD and RGDp-grafted nanoparticles to tumor vessels as well as the
effective retardation of TLT tumor growth and prolonged survival times of mice
treated by PTX-loaded RGD-nanoparticles when compared to non-targeted
nanoparticles. Hence, the targeting of anti-cancer drug to tumor endothelium by
RGD-labeled NP is a promising approach.

PMID: 19699245 [PubMed - in process]