title: Enhanced stability and activity of temozolomide in primary glioblastoma multiforme cells with cucurbit[n]uril.
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.
authors.affiliation: Melville Laboratory for Polymer Synthesis, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Appel
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Rowland
authors.forename: Xian Jun
authors.initials: XJ
authors.lastname: Loh
authors.forename: Richard M
authors.initials: RM
authors.lastname: Heywood
authors.forename: Colin
authors.initials: C
authors.lastname: Watts
authors.forename: Oren A
authors.initials: OA
authors.lastname: Scherman
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D001812:Blood-Brain Barrier / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000737:chemistry*; D002151:Calorimetry; D002470:Cell Survival / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D000077204:Temozolomide; D013816:Thermodynamics; D014407:Tumor Cells, Cultured; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils
chemical_list: D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D003606:Dacarbazine; D004337:Drug Carriers; D007093:Imidazoles; D000077204:Temozolomide; C456276:cucurbit(7)uril; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils