Enhanced stability and activity of temozolomide in primary glioblastoma multiforme cells with cucurbit[n]uril

Research output: Contribution to journalArticle

Authors

  • Eric A Appel
  • Matthew J Rowland
  • Xian Jun Loh
  • Richard M Heywood
  • Oren A Scherman

Colleges, School and Institutes

External organisations

  • University of Cambridge

Abstract

Temozolomide (TMZ) is the primary chemotherapeutic agent for treatment of glioblastoma multiforme (GBM) yet it has a fast rate of degradation under physiological conditions to the 'active' MTIC, which has poor penetration of the blood-brain barrier and cellular absorption. Herein we have demonstrated binding of TMZ within the cavity of nano-container cucurbit[7]uril, resulting in a decreased rate of drug degradation. Prolonging the lifetime of the TMZ under physiological conditions through encapsulation dramatically improved the drug's activity against primary GBM cell lines as more TMZ could be absorbed by the cells before degradation. This work can potentially lead to increases in the drug's propensity for crossing the blood-brain barrier and absorption into the GBM cells, thereby increasing the efficacy of this chemotherapy.

Details

Original languageEnglish
Pages (from-to)9843-5
Number of pages3
JournalChemical communications (Cambridge, England)
Volume48
Issue number79
Publication statusPublished - 11 Oct 2012

Keywords

  • Antineoplastic Agents/chemistry, Blood-Brain Barrier/metabolism, Bridged-Ring Compounds/chemistry, Calorimetry, Cell Survival/drug effects, Dacarbazine/analogs & derivatives, Drug Carriers/chemistry, Glioblastoma/metabolism, Humans, Imidazoles/chemistry, Temozolomide, Thermodynamics, Tumor Cells, Cultured