A novel CD123-targeted therapeutic peptide loaded by micellar delivery system combats refractory acute myeloid leukemia

Abstract Acute myeloid leukemia (AML) is a common malignant heterogeneous hematopoietic disease with very low average 5-year survival rate due to the refractory feature and high rate of relapse. CD123 is highly expressed on multiple types of AML cells, especially leukemia stem cells, and closely ass...

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Autores principales: Shilin Xu, Meichen Zhang, Xiaocui Fang, Jie Meng, Haiyan Xing, Doudou Yan, Jian Liu, Yanlian Yang, Tao Wen, Weiqi Zhang, Jianxiang Wang, Chen Wang, Haiyan Xu
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Publicado: BMC 2021
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Acceso en línea:https://doaj.org/article/0e60652edd234b4d9ef71d32a712ed41
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spelling oai:doaj.org-article:0e60652edd234b4d9ef71d32a712ed412021-11-14T12:05:37ZA novel CD123-targeted therapeutic peptide loaded by micellar delivery system combats refractory acute myeloid leukemia10.1186/s13045-021-01206-y1756-8722https://doaj.org/article/0e60652edd234b4d9ef71d32a712ed412021-11-01T00:00:00Zhttps://doi.org/10.1186/s13045-021-01206-yhttps://doaj.org/toc/1756-8722Abstract Acute myeloid leukemia (AML) is a common malignant heterogeneous hematopoietic disease with very low average 5-year survival rate due to the refractory feature and high rate of relapse. CD123 is highly expressed on multiple types of AML cells, especially leukemia stem cells, and closely associated with the poor prognosis of AML. Aiming to meet the urgent demand to targeted therapeutics for the refractory AML patients, herein we synthesize a CD123 antagonistic peptide (PO-6) loaded in nanomicelles (mPO-6), and investigated its therapeutic effect and pharmacokinetics on a lab-established refractory AML mice model (AE & CKITD816V). It is shown that the PO-6 can effectively bind to the CD123+ AML cells and the micellar formulation mPO-6 increases the dissolution stability and the specific binding capacity. When injected intravenously, mPO-6 significantly prolongs the survival of the refractory AML mice by interfering CD123/IL-3 axis, evidenced by the down regulation of phosphorylation of STAT5 and PI3K/AKT and the inhibition of activated NF-κB in the nucleus, as well as by the analysis results of next generation RNA-sequencing (RNA-seq) with the bone marrow of the AML mice. The antagonistic effect leads to the significantly reduction of AML cells infiltration in the bone marrow of the AML mice. In conclusion, mPO-6 could provide a potent antagonistic therapeutic approach for targeted treatment of AML.Shilin XuMeichen ZhangXiaocui FangJie MengHaiyan XingDoudou YanJian LiuYanlian YangTao WenWeiqi ZhangJianxiang WangChen WangHaiyan XuBMCarticleAcute myeloid leukemiaCD123Antagonistic peptideMicelleTargetingDiseases of the blood and blood-forming organsRC633-647.5Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJournal of Hematology & Oncology, Vol 14, Iss 1, Pp 1-5 (2021)
institution DOAJ
collection DOAJ
language EN
topic Acute myeloid leukemia
CD123
Antagonistic peptide
Micelle
Targeting
Diseases of the blood and blood-forming organs
RC633-647.5
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle Acute myeloid leukemia
CD123
Antagonistic peptide
Micelle
Targeting
Diseases of the blood and blood-forming organs
RC633-647.5
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Shilin Xu
Meichen Zhang
Xiaocui Fang
Jie Meng
Haiyan Xing
Doudou Yan
Jian Liu
Yanlian Yang
Tao Wen
Weiqi Zhang
Jianxiang Wang
Chen Wang
Haiyan Xu
A novel CD123-targeted therapeutic peptide loaded by micellar delivery system combats refractory acute myeloid leukemia
description Abstract Acute myeloid leukemia (AML) is a common malignant heterogeneous hematopoietic disease with very low average 5-year survival rate due to the refractory feature and high rate of relapse. CD123 is highly expressed on multiple types of AML cells, especially leukemia stem cells, and closely associated with the poor prognosis of AML. Aiming to meet the urgent demand to targeted therapeutics for the refractory AML patients, herein we synthesize a CD123 antagonistic peptide (PO-6) loaded in nanomicelles (mPO-6), and investigated its therapeutic effect and pharmacokinetics on a lab-established refractory AML mice model (AE & CKITD816V). It is shown that the PO-6 can effectively bind to the CD123+ AML cells and the micellar formulation mPO-6 increases the dissolution stability and the specific binding capacity. When injected intravenously, mPO-6 significantly prolongs the survival of the refractory AML mice by interfering CD123/IL-3 axis, evidenced by the down regulation of phosphorylation of STAT5 and PI3K/AKT and the inhibition of activated NF-κB in the nucleus, as well as by the analysis results of next generation RNA-sequencing (RNA-seq) with the bone marrow of the AML mice. The antagonistic effect leads to the significantly reduction of AML cells infiltration in the bone marrow of the AML mice. In conclusion, mPO-6 could provide a potent antagonistic therapeutic approach for targeted treatment of AML.
format article
author Shilin Xu
Meichen Zhang
Xiaocui Fang
Jie Meng
Haiyan Xing
Doudou Yan
Jian Liu
Yanlian Yang
Tao Wen
Weiqi Zhang
Jianxiang Wang
Chen Wang
Haiyan Xu
author_facet Shilin Xu
Meichen Zhang
Xiaocui Fang
Jie Meng
Haiyan Xing
Doudou Yan
Jian Liu
Yanlian Yang
Tao Wen
Weiqi Zhang
Jianxiang Wang
Chen Wang
Haiyan Xu
author_sort Shilin Xu
title A novel CD123-targeted therapeutic peptide loaded by micellar delivery system combats refractory acute myeloid leukemia
title_short A novel CD123-targeted therapeutic peptide loaded by micellar delivery system combats refractory acute myeloid leukemia
title_full A novel CD123-targeted therapeutic peptide loaded by micellar delivery system combats refractory acute myeloid leukemia
title_fullStr A novel CD123-targeted therapeutic peptide loaded by micellar delivery system combats refractory acute myeloid leukemia
title_full_unstemmed A novel CD123-targeted therapeutic peptide loaded by micellar delivery system combats refractory acute myeloid leukemia
title_sort novel cd123-targeted therapeutic peptide loaded by micellar delivery system combats refractory acute myeloid leukemia
publisher BMC
publishDate 2021
url https://doaj.org/article/0e60652edd234b4d9ef71d32a712ed41
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