| Autor: |
Yifeng Xia, Jingnan An, Jiaying Li, Wenxing Gu, Yifan Zhang, Songsong Zhao, Cenzhu Zhao, Yang Xu, Bin Li, Zhiyuan Zhong, Fenghua Meng |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Bioactive Materials, Vol 21, Iss , Pp 499-510 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2452-199X |
| DOI: |
10.1016/j.bioactmat.2022.08.032 |
| Popis: |
Acute myeloid leukemia (AML) remains a most lethal hematological malignancy, partly because of its slow development of targeted therapies compared with other cancers. PLK1 inhibitor, volasertib (Vol), is among the few molecular targeted drugs granted breakthrough therapy status for AML; however, its fast clearance and dose-limiting toxicity greatly restrain its clinical benefits. Here, we report that transferrin-guided polymersomes (TPs) markedly augment the targetability, potency and safety of Vol to AML. Vol-loaded TPs (TPVol) with 4% transferrin exhibited best cellular uptake, effective down-regulation of p-PLK1, p-PTEN and p-AKT and superior apoptotic activity to free Vol in MV-4-11 leukemic cells. Intravenous injection of TPVol gave 6-fold higher AUC than free Vol and notable accumulation in AML-residing bone marrow. The efficacy studies in orthotopic MV-4-11 leukemic model demonstrated that TPVol significantly reduced leukemic cell proportions in periphery blood, bone marrow, liver and spleen, effectively enhanced mouse survival rate, and impeded bone loss. This transferrin-guided nano-delivery of molecular targeted drugs appears to be an interesting strategy towards the development of novel treatments for AML. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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