2. Academic Validation
  3. Identification of Novel Medulloblastoma Cell-Targeting Peptides for Use in Selective Chemotherapy Drug Delivery

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

  • J Med Chem. 2020 Mar 12;63(5):2181-2193. doi: 10.1021/acs.jmedchem.9b00851.
Kristel C Tjandra 1 2,  Nigel McCarthy 3,  Lu Yang 3,  Alistair J Laos 1 2,  George Sharbeen 4,  Phoebe A Phillips 1 4,  Helen Forgham 3 1 5,  Sharon M Sagnella 3,  Renee M Whan 1 6,  Maria Kavallaris 3 1 5,  Pall Thordarson 1 2,  Joshua A McCarroll 3 1 5
Affiliations

Affiliations

  • 1 Australian Centre for Nanomedicine, ARC Centre of Excellence in Convergent Bio-Nano Science & Technology, UNSW Sydney, Sydney, NSW 2052, Australia.
  • 2 School of Chemistry, UNSW Sydney, Sydney, NSW 2052, Australia.
  • 3 Tumour Biology & Targeting Program, Children's Cancer Institute, UNSW Sydney, Lowy Cancer Research Centre, Sydney, NSW 2031, Australia.
  • 4 Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, and School of Medical Sciences, UNSW Sydney, Sydney, NSW 2052, Australia.
  • 5 School of Women's and Children's Health, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2052, Australia.
  • 6 Biomedical Imaging Facility Mark Wainwright Analytical Centre, UNSW Sydney, Sydney, NSW 2052, Australia.
PMID: 31347843 DOI: 10.1021/acs.jmedchem.9b00851
Abstract

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.

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