title: Targeting of tumor endothelium by RGD-grafted PLGA-nanoparticles loaded with paclitaxel.
abstract: 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.
authors.affiliation: Université Catholique de Louvain, Unité de Pharmacie Galénique, Avenue Mounier 73-20, 1200 Brussels, Belgium.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Danhier
authors.forename: Benoît
authors.initials: B
authors.lastname: Vroman
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lecouturier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Crokart
authors.forename: Vincent
authors.initials: V
authors.lastname: Pourcelle
authors.forename: Hélène
authors.initials: H
authors.lastname: Freichels
authors.forename: Christine
authors.initials: C
authors.lastname: Jérôme
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Marchand-Brynaert
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D042783:Endothelial Cells / Q000378:metabolism*; D005026:Ethylene Glycols / Q000737:chemistry; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D017239:Paclitaxel / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011091:Polyesters / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D005026:Ethylene Glycols; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D011091:Polyesters; C476300:poly(epsilon-caprolactone)-b-poly(ethylene glycol); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C047981:arginyl-glycyl-aspartic acid; D017239:Paclitaxel