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Targeting Of Tumor Endothelium By RGD-grafted PLGA-nanoparticles Loaded With Paclitaxel.
F. Danhier, B. Vroman, N. Lecouturier, N. Crokart, V. Pourcelle, H. Freichels, C. Jérôme, J. Marchand-Brynaert, O. Féron, V. Préat
Published 2009 · Medicine, Chemistry
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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.
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