[en] 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 αvβ3 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.
Research center :
Center for Education and Research on Macromolecules (CERM)
Disciplines :
Materials science & engineering Chemistry
Author, co-author :
Danhier, Fabienne; Université catholique de Louvain (UCL), Bruxelles > Unité de Pharmacie Galénique
Vroman, Benoît; Université catholique de Louvain (UCL), Bruxelles > Unité de Pharmacie Galénique
Lecouturier, Nathalie; Université catholique de Louvain (UCL), Bruxelles > Unité de Pharmacie Galénique
Crokart, Nathalie; Université catholique de Louvain (UCL), Bruxelles > Unité de Pharmacie Galénique
Pourcelle, Vincent; Université catholique de Louvain (UCL) > Unité de Chimie Organique et Médicinale
Freichels, Hélène ; Université de Liège - ULiège > Department of Chemistry > Center for Education and Research on Macromolecules (CERM)
Jérôme, Christine ; Université de Liège - ULiège > Department of Chemistry > Center for Education and Research on Macromolecules (CERM)
Marchand-Brynaert, Jacqueline; Université catholique de Louvain (UCL) > Unité de Chimie Organique et Médicinale
Feron, Olivier; Université catholique de Louvain (UCL), Bruxelles > Laboratoire de Pharmacologie et de Thérapeutique
Préat, Véronique; Université catholique de Louvain (UCL), Bruxelles > Unité de Pharmacie Galénique
Language :
English
Title :
Targeting of tumor endothelium by RGD-grafted PLGA-nanoparticles loaded with Paclitaxel
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