Paclitaxel-loaded multifunctional nanoparticles for the targeted treatment of glioblastoma. (3rd July 2019)

• Record Type: Journal Article
• Authors: Ganipineni, Lakshmi Pallavi; Ucakar, Bernard; Joudiou, Nicolas; Riva, Raphaël; Jérôme, Christine; Gallez, Bernard; Danhier, Fabienne; Préat, Véronique
• Is Part Of: Journal of drug targeting. Volume 27:Number 5/6(2019)
• Page Start: 614
• Page End: 623
• Publication Date: 2019-07-03
• Subjects: PLGA nanoparticles -- glioblastoma -- targeting -- nanomedicine -- nanotheranostics -- paclitaxel; Drug delivery systems -- Periodicals; Drug Delivery Systems; Vehicles; Drug Administration Routes; Drug Evaluation; 615.7
• DOI: 10.1080/1061186X.2019.1567738
• Languages: English
• ISSNs: 1061-186X

Abstract

Abstract: Introduction: We hypothesised 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 tumour and therefore improve the treatment of GBM. Methods: PTX/SPIO PLGA nanoparticles with or without RGD-grafting were characterised. Their in vitro cellular uptake and cytotoxicity was evaluated by fluorospectroscopy and MTT assay. In vivo safety and anti-tumour efficacy of different targeting strategies were evaluated in orthotopic U87MG tumour model over multiple intravenous injections. Results: The nanoparticles of 250 nm 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 48 h was ∼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 a better therapeutic effect than the other targeting strategies (passive, active).