Paclitaxel-loaded multifunctional nanoparticles for the targeted treatment of glioblastoma

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Cell Line
  • Cell Line, Tumor
  • Drug Carriers / chemistry
  • Female
  • Glioblastoma / drug therapy*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Integrin alphaVbeta3 / metabolism
  • Magnetics / methods
  • Mice
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Paclitaxel / chemistry*
  • Paclitaxel / pharmacology*
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Tissue Distribution / drug effects
  • Xenograft Model Antitumor Assays / methods

Substances

  • Antineoplastic Agents, Phytogenic
  • Drug Carriers
  • Integrin alphaVbeta3
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Paclitaxel