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.