Development of a magnetic nano-graphene oxide carrier for improved glioma-targeted drug delivery and imaging: In vitro and in vivo evaluations

Chem Biol Interact. 2018 Nov 1;295:97-108. doi: 10.1016/j.cbi.2018.08.027. Epub 2018 Aug 28.

Abstract

To overcome the obstacles inflicted by the BBB in Glioblastoma multiforme (GBM) we investigated the use of Multifunctional nanoparticles that designed with a Nano-graphene oxide (NGO) sheet functionalized with magnetic poly (lactic-co-glycolic acid) (PLGA) and was used for glioma targeting delivery of radiosensitizing 5-iodo-2-deoxyuridine (IUdR). In vitro biocompatibility of nanocomposite has been studied by the MTT assay. In vivo efficacy of magnetic targeting on the amount and selectivity of magnetic nanoparticles accumulation in glioma-bearing rats under an external magnetic field (EMF) density of 0.5 T was easily monitored with MRI. IUdR-loaded magnetic NGO/PLGA with a diameter of 71.8 nm, a zeta potential of -33.07 ± 0.07 mV, and a drug loading content of 3.04 ± 0.46% presented superior superparamagnetic properties with a saturation magnetization (Ms) of 15.98 emu/g. Furthermore, Prussian blue staining showed effective magnetic targeting, leading to remarkably improved tumor inhibitory efficiency of IUdR. The tumor volume of rats after treatment with IUdR/NGO/SPION/PLGA + MF was decreased significantly compared to the rats treated with buffer saline, IUdR and SPION/IUdR/NGO/PLGA. Most importantly, our data demonstrate that IUdR/NGO/SPION/PLGA at the present magnetic field prolongs the median survival time of animals bearing gliomas (38 days, p < 0.01). Nanoparticles also had high thermal sensitivities under the alternating magnetic field. In conclusion, we developed magnetic IUdR/NGO/PLGA, which not only achieved to high accumulation at the targeted tumor site by magnetic targeting but also indicated significantly enhanced therapeutic efficiency and toxicity for glioma both in vitro and in vivo. This innovation increases the possibility of improving clinical efficiency of IUdR as a radiosensitizer, or lowering the total drug dose to decrease systemic toxicity.

Keywords: 5-Iodo-2′-deoxyuridine; Glioma; Magnetic targeting; Nano-graphene oxide; Superparamagnetic iron oxide.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacology
  • Drug Delivery Systems*
  • Drug Screening Assays, Antitumor
  • Glioma / diagnostic imaging
  • Glioma / drug therapy*
  • Glioma / pathology
  • Graphite / chemistry
  • Graphite / pharmacology
  • Magnetic Resonance Imaging
  • Magnetite Nanoparticles / chemistry
  • Male
  • Optical Imaging*
  • Oxides / chemistry
  • Oxides / pharmacology
  • Particle Size
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer / pharmacology
  • Rats
  • Rats, Wistar
  • Tumor Cells, Cultured
  • Uridine / analogs & derivatives
  • Uridine / chemistry
  • Uridine / pharmacology

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Magnetite Nanoparticles
  • Oxides
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Graphite
  • Uridine