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J Drug Target. 2019 Jun - Jul;27(5-6):614-623. doi: 10.1080/1061186X.2019.1567738. Epub 2019 Jan 24.

Paclitaxel-loaded multifunctional nanoparticles for the targeted treatment of glioblastoma.

Author information

1
a Université Catholique de Louvain, Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute ,   Brussels , Belgium.
2
b Université Catholique de Louvain, Nuclear and Electron Spin Technologies Platform (NEST), Louvain Drug Research Institute , Brussels , Belgium.
3
c University of Liège, Center for Education and Research on Macromolecules (CERM), CESAM Research Unit , Liège , Belgium.

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).

KEYWORDS:

PLGA nanoparticles; glioblastoma; nanomedicine; nanotheranostics; paclitaxel; targeting

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