Paclitaxel-loaded multifunctional nanoparticles for the targeted treatment of glioblastoma

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
• targeting
• nanomedicine
• nanotheranostics
• paclitaxel

Acknowledgements

We express our thanks to Kevin Vanvarenberg (Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, Belgium) for his help with histology.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

We gratefully acknowledge Télévie, Belgian Fonds National de la Recherche Scientifique (FRS-FNRS) [7651916F], Fondation contre le cancer and Stichting Tegen Kanker (Fondation contre le cancer) for funding this work.