[en] We hypothesized that the active targeting of αvβ3 integrin overexpressed in neoangiogenic blood vessels and glioblastoma (GBM) cells combined with magnetic targeting of paclitaxel- and SPIO-loaded PLGA-based nanoparticles could improve accumulation of nanoparticles in the tumor and therefore improve the treatment of GBM. Methods: PTX/SPIO PLGA nanoparticles with or without RGD-grafting were characterized. Their in vitro cellular uptake and cytotoxicity was evaluated by fluorospectroscopy and MTT assay. In vivo safety and anti-tumor efficacy of different targeting strategies was evaluated in orthotopic U87MG tumor model over multiple intravenous injections. Results: The nanoparticles of 250nm were negatively charged. RGD targeted nanoparticles showed a specific and higher cellular uptake than untargeted nanoparticles by activated U87MG and HUVEC cells. In vitro IC50 of PTX after 48h was approximately 1 ng/mL for all the PTX-loaded nanoparticles. The median survival time of the mice treated with magnetic targeted nanoparticles was higher than the control (saline) mice or mice treated with other evaluated strategies. The 6 doses of PTX did not induce any detectable toxic effects on liver, kidney and heart when compared to Taxol. Conclusion. The magnetic targeting strategy resulted in better therapeutic effect than the other targeting strategies (passive, active).
Research center :
CESAM - Complex and Entangled Systems from Atoms to Materials - ULiège Center for Education and Research on Macromolecules (CERM)
Disciplines :
Materials science & engineering Chemistry
Author, co-author :
Ganipineni, Lakshmi Pallavi; Université catholique de Louvain (UCL), Brussels, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials
Ucakar, Bernard; Université catholique de Louvain (UCL), Brussels, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials
Joudiou, Nicolas; Université catholique de Louvain (UCL), Brussels, Louvain Drug Research Institute, Nuclear and Electron Spin Technologies Platform (NEST)
Riva, Raphaël ; University of Liège (ULiège), Complex and Entangled Systems from Atoms to Materials (CESAM), Center for Education and Research on Macromolecules (CERM)
Jérôme, Christine ; University of Liège (ULiège), Complex and Entangled Systems from Atoms to Materials (CESAM), Center for Education and Research on Macromolecules (CERM)
Gallez, Bernard; Université catholique de Louvain (UCL), Brussels, Louvain Drug Research Institute, Nuclear and Electron Spin Technologies Platform (NEST)
Danhier, Fabienne; Université catholique de Louvain (UCL), Brussels, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials
Préat, Véronique; Université catholique de Louvain (UCL), Brussels, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials
Language :
English
Title :
Paclitaxel-loaded multifunctional nanoparticles for the targeted treatment of glioblastoma
Publication date :
2019
Journal title :
Journal of Drug Targeting
ISSN :
1061-186X
eISSN :
1029-2330
Publisher :
Taylor & Francis, United Kingdom
Volume :
27
Issue :
5-6
Pages :
614-623
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] Télévie [BE] Fondation contre le Cancer [BE]
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