Identification of Novel Medulloblastoma Cell-Targeting Peptides for Use in Selective Chemotherapy Drug Delivery

Medulloblastoma is
a malignant brain tumor diagnosed in children.
Chemotherapy has improved survival rates to approximately 70%; however,
children are often left with long-term treatment side effects. New
therapies that maintain a high cure rate while reducing off-target
toxicity are required. We describe for the first time the use of a
bacteriophage-peptide display library to identify heptapeptides that
bind to medulloblastoma cells. Two heptapeptides that demonstrated
high [E1-3 (1)] or low [E1-7 (2)] medulloblastoma
cell binding affinity were synthesized. The potential of the peptides
to deliver a therapeutic drug to medulloblastoma cells with specificity
was investigated by conjugating E1-3 (1) or E1-7 (2) to doxorubicin (5). Both peptide–drug
conjugates were cytotoxic to medulloblastoma cells. E1-3 doxorubicin
(3) could permeabilize an in vitro blood–brain
barrier and showed a marked reduction in cytotoxicity compared to
free doxorubicin (5) in nontumor cells. This study provides
proof-of-concept for developing peptide–drug conjugates to
inhibit medulloblastoma cell growth while minimizing off-target toxicity.