Poly(ethylene glycol) based nanotubes for tuneable drug delivery to glioblastoma multiforme

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Majed Alghamdi - , Cardiff University, King Abdulaziz University (Author)
  • Filippo Chierchini - , Cardiff University (Author)
  • Dimitri Eigel - , Chair of Biofunctional Polymer Materials, Leibniz Institute of Polymer Research Dresden (Author)
  • Christian Taplan - , Leibniz Institute of Polymer Research Dresden (Author)
  • Thomas Miles - , Cardiff University (Author)
  • Dagmar Pette - , Leibniz Institute of Polymer Research Dresden (Author)
  • Petra B. Welzel - , Leibniz Institute of Polymer Research Dresden (Author)
  • Carsten Werner - , Chair of Biofunctional Polymer Materials, Leibniz Institute of Polymer Research Dresden (Author)
  • Wenxin Wang - , University College Dublin (Author)
  • Catia Neto - , Cardiff University (Author)
  • Mark Gumbleton - , Cardiff University (Author)
  • Ben Newland - , Cardiff University, Leibniz Institute of Polymer Research Dresden (Author)

Abstract

Glioblastoma multiforme (GBM) is the most aggressive type of malignant brain tumour, which is associated with a poor two-year survival rate and a high rate of fatal recurrence near the original tumour. Focal/local drug delivery devices hold promise for improving therapeutic outcomes for GBM by increasing drug concentrations locally at the tumour site, or by facilitating the use of potent anti-cancer drugs that are poorly permeable across the blood brain barrier (BBB). For inoperable tumours, stereotactic delivery to the tumour necessitates the development of nanoscale/microscale injectable drug delivery devices. Herein we assess the ability of a novel class of polymer nanotube (based on poly(ethylene glycol) (PEG)) to load doxorubicin (a mainstay breast cancer therapeutic with poor BBB permeability) and release it slowly. The drug loading properties of the PEG nanotubes could be tuned by varying the degree of carboxylic acid functionalisation and hence the capacity of the nanotubes to electrostatically bind and load doxorubicin. 70% of the drug was released over the first seven days followed by sustained drug release for the remaining two weeks tested. Unloaded PEG nanotubes showed no toxicity to any of the cell types analysed, whereas doxorubicin loaded nanotubes decreased GBM cell viability (C6, U-87 and U-251) in a dose dependent manner in 2Din vitroculture. Finally, doxorubicin loaded PEG nanotubes significantly reduced the viability ofin vitro3D GBM models whilst unloaded nanotubes showed no cytotoxicity. Taken together, these findings show that polymer nanotubes could be used to deliver alternative anti-cancer drugs for local therapeutic strategies against brain cancers.

Details

Original languageEnglish
Pages (from-to)4498-4509
Number of pages12
JournalNanoscale advances
Volume2
Issue number10
Publication statusPublished - Oct 2020
Peer-reviewedYes

External IDs

ORCID /0000-0003-0189-3448/work/161890289