A targeted combinatorial therapy for Ewing's sarcoma.
A targeted combinatorial therapy for Ewing's sarcoma.
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DOI：
10.1016/j.nano.2021.102446
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Taratula O
中科院分区：
文献类型：
--
作者：
Sabei FY;Taratula O;Albarqi HA;Al-Fatease AM;Moses AS;Demessie AA;Park Y;Vogel WK;Esfandiari Nazzaro E;Davare MA;Alani A;Leid M;Taratula O
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. We have developed a targeted combinatorial therapy for Ewing’s sarcoma (EwS) based on a novel drug candidate named ML111. This molecule exhibits a robust synergistic effect in combination with vincristine on EwS cells, while the same drug pair provides antagonistic effects towards nonmalignant cells. To enhance the translational potential of this combinatorial therapy regimen, we prepared ML111-loaded nanoparticles that efficiently accumulate in orthotopic EwS xenografts following systemic administration and induce marked regression of these tumors in combination with vincristine.
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影响因子：
3.7
作者：
Schreinemacher MH;Backes WH;Slenter JM;Xanthoulea S;Delvoux B;van Winden L;Beets-Tan RG;Evers JL;Dunselman GA;Romano A
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DOI：
10.1016/j.jconrel.2013.04.018
发表时间：
2013-11-10
期刊：
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影响因子：
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DOI：
10.1158/1078-0432.ccr-15-2624
发表时间：
2016-08-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
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作者：
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