title: Treatment of glioblastoma multiforme cells with temozolomide-BioShuttle ligated by the inverse Diels-Alder ligation chemistry.
abstract: Recurrent glioblastoma multiforme (GBM), insensitive against most therapeutic interventions, has low response and survival rates. Temozolomide (TMZ) was approved for second-line therapy of recurrent anaplastic astrocytoma. However, TMZ therapy in GBM patients reveals properties such as reduced tolerability and inauspicious hemogram. The solution addressed here concerning GBM therapy consolidates and uses the potential of organic and peptide chemistry with molecular medicine. We enhanced the pharmacologic potency with simultaneous reduction of unwanted adverse reactions of the highly efficient chemotherapeutic TMZ. The TMZ connection to transporter molecules (TMZ-BioShuttle) was investigated, resulting in a much higher pharmacological effect in glioma cell lines and also with reduced dose rate. From this result we can conclude that a suitable chemistry could realize the ligation of pharmacologically active, but sensitive and highly unstable pharmaceutical ingredients without functional deprivation. The TMZ-BioShuttle dramatically enhanced the potential of TMZ for the treatment of brain tumors and is an attractive drug for combination chemotherapy.
authors.affiliation: German Cancer Research Center, Dept of Imaging and Radiooncology, Im Neuenheimer Feld 280, Heidelberg, Germany. k.braun@dkfz.de
authors.forename: Klaus
authors.initials: K
authors.lastname: Braun
authors.forename: Manfred
authors.initials: M
authors.lastname: Wiessler
authors.forename: Volker
authors.initials: V
authors.lastname: Ehemann
authors.forename: Ruediger
authors.initials: R
authors.lastname: Pipkorn
authors.forename: Herbert
authors.initials: H
authors.lastname: Spring
authors.forename: Juergen
authors.initials: J
authors.lastname: Debus
authors.forename: Bernd
authors.initials: B
authors.lastname: Didinger
authors.forename: Mario
authors.initials: M
authors.lastname: Koch
authors.forename: Gabriele
authors.initials: G
authors.lastname: Muller
authors.forename: Waldemar
authors.initials: W
authors.lastname: Waldeck