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

doi:10.1016/j.nano.2021.102446

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

Pediatric Hematology and Oncology

Research output: Contribution to journal › Article › peer-review

5 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 language	English (US)
Article number	102446
Journal	Nanomedicine: Nanotechnology, Biology, and Medicine
Volume	37
DOIs	https://doi.org/10.1016/j.nano.2021.102446
State	Published - Oct 2021

Keywords

Chemotherapy
Combinatorial therapy
Ewing's sarcoma
ML111
Nanoparticle

ASJC Scopus subject areas

Bioengineering
Medicine (miscellaneous)
Molecular Medicine
Biomedical Engineering
General Materials Science
Pharmaceutical Science

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Sabei, F. Y., Taratula, O., Albarqi, H. A., Al-Fatease, A. M., Moses, A. S., Demessie, A. A., Park, Y., Vogel, W. K., Esfandiari Nazzaro, E., Davare, M. A., Alani, A., Leid, M., & Taratula, O. (2021). A targeted combinatorial therapy for Ewing's sarcoma. Nanomedicine: Nanotechnology, Biology, and Medicine, 37, Article 102446. https://doi.org/10.1016/j.nano.2021.102446

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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.",

keywords = "Chemotherapy, Combinatorial therapy, Ewing's sarcoma, ML111, Nanoparticle",

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

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year = "2021",

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doi = "10.1016/j.nano.2021.102446",

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AU - Taratula, Olena

AU - Albarqi, Hassan A.

AU - Al-Fatease, Adel M.

AU - Moses, Abraham S.

AU - Demessie, Ananiya A.

AU - Park, Youngrong

AU - Vogel, Walter K.

AU - Esfandiari Nazzaro, Ellie

AU - Davare, Monika A.

AU - Alani, Adam

AU - Leid, Mark

AU - Taratula, Oleh

PY - 2021/10

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N2 - 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.

AB - 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.

KW - Chemotherapy

KW - Combinatorial therapy

KW - Ewing's sarcoma

KW - ML111

KW - Nanoparticle

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A targeted combinatorial therapy for Ewing's sarcoma

Abstract

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