A targeted combinatorial therapy for Ewing's sarcoma

Fahad Y. Sabei, Olena Taratula, Hassan A. Albarqi, Adel M. Al-Fatease, Abraham S. Moses, Ananiya A. Demessie, Youngrong Park, Walter K. Vogel, Ellie Esfandiari Nazzaro, Monika A. Davare, Adam Alani, Mark Leid, Oleh Taratula

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Ewing's sarcoma (EwS) is the second most common bone cancer in children and adolescents. Current chemotherapy regimens are mainly ineffective in patients with relapsed disease and cause long-term effects in survivors. Therefore, we have developed a combinatorial therapy based on a novel drug candidate named ML111 that exhibits selective activity against EwS cells and synergizes with vincristine. To increase the aqueous solubility of hydrophobic ML111, polymeric nanoparticles (ML111-NP) were developed. In vitro data revealed that ML111-NP compromise viability of EwS cells without affecting non-malignant cells. Furthermore, ML111-NP exhibit strong synergistic effects in a combination with vincristine on EwS cells, while this drug pair exhibits antagonistic effects towards normal cells. Finally, animal studies validated that ML111-NP efficiently accumulate in orthotopic EwS xenografts after intravenous injection and provide superior therapeutic outcomes in a combination with vincristine without evident toxicity. These results support the potential of the ML111-based combinatorial therapy for EwS.

Original languageEnglish (US)
Article number102446
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume37
DOIs
StatePublished - Oct 2021

Keywords

  • Chemotherapy
  • Combinatorial therapy
  • Ewing's sarcoma
  • ML111
  • Nanoparticle

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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