Co-delivery of homoharringtonine and doxorubicin boosts therapeutic efficacy of refractory acute myeloid leukemia
| Autor: | Jian Liu, Hui Wei, Jie Meng, Yangyang Ge, Tao Wen, Jianxiang Wang, Shilin Xu, Haiyan Xu, Doudou Yan, Xinning Lai, Weiqi Zhang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
HL60
Pharmaceutical Science Apoptosis 02 engineering and technology Mice 03 medical and health sciences chemistry.chemical_compound hemic and lymphatic diseases Antineoplastic Combined Chemotherapy Protocols medicine Animals Doxorubicin 030304 developmental biology 0303 health sciences business.industry Therapeutic effect Myeloid leukemia 021001 nanoscience & nanotechnology medicine.disease Leukemia Myeloid Acute Leukemia medicine.anatomical_structure chemistry Homoharringtonine Toxicity Cancer research Bone marrow 0210 nano-technology business medicine.drug |
| Zdroj: | Journal of Controlled Release. 327:766-778 |
| ISSN: | 0168-3659 |
| Popis: | Refractory acute myeloid leukemia (AML) remains a challenging hematological malignancy to treat, due to the development of drug resistance, severe complications, and relapse in chemotherapies. Free-drugs combination has demonstrated enhanced therapeutic efficacy in AML, while it requires complicated administration regimens and brings added toxicity. To tackle this complex disease, in this work two clinically applied therapeutics, doxorubicin and homoharringtonine, were assembled into one polymeric micelle to form a co-delivery system (DHM) to facilitate a novel and simple administration regimen. The DHM was systematically investigated in the drug-resistant AML cell line HL60/A as well as in the AML1-ETO+-c-kit+ mouse featuring as a refractory and relapsed AML model following comprehensive characterizations. Compared with the free-drugs combination, DHM significantly enhanced the cellular uptake of the therapeutics, inhibited the cell division and induced a higher rate of cells apoptosis in vitro. More importantly, the intraperitoneal injection of DHM remarkably eradicated leukemia cells in the peripheral blood, bone marrow, spleen and liver of the AML mice and significantly prolonged the survival of the mice without additional systematic toxicity compared with that of the free-drugs combination. In conclusion, the DHM boosted the therapeutic effect of clinically applied chemodrugs as well as provided a novel platform for multi-drugs co-delivery against refractory and relapsed AML, therefore holding promising potential for translational medicine. |
| Databáze: | OpenAIRE |
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