التفاصيل البيبلوغرافية
| العنوان: |
A Nucleus-Targeting WT1 Antagonistic Peptide Encapsulated in Polymeric Nanomicelles Combats Refractory Chronic Myeloid Leukemia. |
| المؤلفون: |
Chen, Mengting1,2 (AUTHOR) chenmt2019@nanoctr.cn, Fang, Xiaocui1,2 (AUTHOR) fangxc@nanoctr.cn, Du, Rong1,2 (AUTHOR) dur2018@nanoctr.cn, Meng, Jie1,2 (AUTHOR) mengj@nanoctr.cn, Liu, Jingyi1,2 (AUTHOR) liujingyi2019@nanoctr.cn, Liu, Mingpeng1,2,3 (AUTHOR) liump2018@nanoctr.cn, Yang, Yanlian1,2 (AUTHOR) yangyl@nanoctr.cn, Wang, Chen1,2 (AUTHOR) yangyl@nanoctr.cn |
| المصدر: |
Pharmaceutics. Sep2023, Vol. 15 Issue 9, p2305. 17p. |
| مصطلحات موضوعية: |
*CHRONIC myeloid leukemia, *PEPTIDES, *NEPHROBLASTOMA, *MYELOPROLIFERATIVE neoplasms, *THROMBOPOIETIN receptors, *SUBCUTANEOUS injections |
| مستخلص: |
Chronic myeloid leukemia (CML) is recognized as a classic clonal myeloproliferative disorder. Given the limited treatment options for CML patients in the accelerated phase (AP) and blast phase (BP), there is an evident need to develop new therapeutic strategies. This has the potential to improve outcomes for individuals in the advanced stages of CML. A promising therapeutic target is Wilms' tumor 1 (WT1), which is highly expressed in BP-CML cells and plays a crucial role in CML progression. In this study, a chemically synthesized nucleus-targeting WT1 antagonistic peptide termed WIP2W was identified. The therapeutic implications of both the peptide and its micellar formulation, M—WIP2W, were evaluated in WT1+ BP-CML cell lines and in mice. The findings indicate that WIP2W can bind specifically to the WT1 protein, inducing cell cycle arrest and notable cytotoxicity in WT1+ BP-CML cells. Moreover, subcutaneous injections of M—WIP2W were observed to significantly enhance intra-tumoral accumulation and to effectively inhibit tumor growth. Thus, WIP2W stands out as a potent and selective WT1 inhibitor, and the M—WIP2W nanoformulation appears promising for the therapeutic treatment of refractory CML as well as other WT1-overexpressing malignant cancers. [ABSTRACT FROM AUTHOR] |
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