Daunorubicin-Loaded CdTe QDs Conjugated with Anti-CD123 mAbs: A Novel Delivery System for Myelodysplastic Syndromes Treatment

Dan Guo,1,2 Peipei Xu,1 Dangui Chen,1 Lili Wang,1 Yudi Zhu,1 Yifan Zuo,1 Bing Chen1 1Department of Hematology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210093, People’s Republic of China; 2Department of Hematology, The Affi...

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Autores principales:	Guo D, Xu P, Chen D, Wang L, Zhu Y, Zuo Y, Chen B
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	myelodysplastic syndrome daunorubicin cdte anti-cd123 monoclonal antibody drug delivery system Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c92989a988ce4d08905da43b89726273
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spelling	oai:doaj.org-article:c92989a988ce4d08905da43b897262732021-12-02T06:43:47ZDaunorubicin-Loaded CdTe QDs Conjugated with Anti-CD123 mAbs: A Novel Delivery System for Myelodysplastic Syndromes Treatment1178-2013https://doaj.org/article/c92989a988ce4d08905da43b897262732020-01-01T00:00:00Zhttps://www.dovepress.com/daunorubicin-loaded-cdte-qds-conjugated-with-anti-cd123-mabs-a-novel-d-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Dan Guo,1,2 Peipei Xu,1 Dangui Chen,1 Lili Wang,1 Yudi Zhu,1 Yifan Zuo,1 Bing Chen1 1Department of Hematology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210093, People’s Republic of China; 2Department of Hematology, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, People’s Republic of ChinaCorrespondence: Bing ChenDepartment of Hematology, Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210093, People’s Republic of ChinaEmail chenbing2004@126.comIntroduction: The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increase risk of transformation to acute myeloid leukemia (AML). Daunorubicin (DNR) is an indispensable drug for the treatment of MDS and AML. However, its side effects including cardiac toxicity and bone marrow suppression severely limit clinical application. Many researches reported high expression of CD123 antigen on high-risk MDS cells, so we constructed a novel drug delivery system comprising daunorubicin-loaded CdTe QDs conjugated with anti-CD123 mAbs (DNR-CdTe-CD123) to develop targeted combination chemotherapy for MDS.Methods: CdTe conjugated antiCD123 through amide bond, co-loaded with DNR with electrostatic bonding. Then, we determined characterization and release rate of DNR-CdTe-CD123. The therapeutic effect and side effect of drug delivery system were evaluated through in vitro and in vivo experiments.Results: CdTe showed appropriate diameter and good dispersibility and DNR was loaded into CdTes with high encapsulation efficiency and drug loading. The maximum drug loading and encapsulation efficiency were 42.08 ± 0.64% and 74.52 ± 1.81%, respectively, at DNR concentration of 0.2mg/mL and anti-CD123 mAbs volume of 5ul (100ug/mL). Flow cytometry (FCM) showed that CD123 antigen was highly expressed on MUTZ-1 cells, and its expression rate was 72.89 ± 10.67%. In vitro experiments showed that the inhibition rate and apoptosis rate of MUTZ-1 cells treated with DNR-CdTe-CD123 were higher than those in the other groups (P< 0.05). Compared with the other groups, the level of apoptosis-related protein (P53, cleaved caspase-9, Bax and cleaved caspase-3) were upregulated in DNR-CdTe-CD123 group (P< 0.05). In vivo experiments, DNR-CdTe-CD123 can effectively inhibit the tumor growth of MDS-bearing nude mice and reduce the side effects of DNR on myocardial cells.Conclusion: The system of DNR-CdTe-CD123 enhances the therapeutic effects and reduce the side effects of DNR, thus providing a novel platform for MDS treatment.Keywords: myelodysplastic syndrome, daunorubicin, CdTe, anti-CD123 monoclonal antibody, drug delivery systemGuo DXu PChen DWang LZhu YZuo YChen BDove Medical Pressarticlemyelodysplastic syndromedaunorubicincdteanti-cd123 monoclonal antibodydrug delivery systemMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 521-536 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	myelodysplastic syndrome daunorubicin cdte anti-cd123 monoclonal antibody drug delivery system Medicine (General) R5-920
spellingShingle	myelodysplastic syndrome daunorubicin cdte anti-cd123 monoclonal antibody drug delivery system Medicine (General) R5-920 Guo D Xu P Chen D Wang L Zhu Y Zuo Y Chen B Daunorubicin-Loaded CdTe QDs Conjugated with Anti-CD123 mAbs: A Novel Delivery System for Myelodysplastic Syndromes Treatment
description	Dan Guo,1,2 Peipei Xu,1 Dangui Chen,1 Lili Wang,1 Yudi Zhu,1 Yifan Zuo,1 Bing Chen1 1Department of Hematology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210093, People’s Republic of China; 2Department of Hematology, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, People’s Republic of ChinaCorrespondence: Bing ChenDepartment of Hematology, Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210093, People’s Republic of ChinaEmail chenbing2004@126.comIntroduction: The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increase risk of transformation to acute myeloid leukemia (AML). Daunorubicin (DNR) is an indispensable drug for the treatment of MDS and AML. However, its side effects including cardiac toxicity and bone marrow suppression severely limit clinical application. Many researches reported high expression of CD123 antigen on high-risk MDS cells, so we constructed a novel drug delivery system comprising daunorubicin-loaded CdTe QDs conjugated with anti-CD123 mAbs (DNR-CdTe-CD123) to develop targeted combination chemotherapy for MDS.Methods: CdTe conjugated antiCD123 through amide bond, co-loaded with DNR with electrostatic bonding. Then, we determined characterization and release rate of DNR-CdTe-CD123. The therapeutic effect and side effect of drug delivery system were evaluated through in vitro and in vivo experiments.Results: CdTe showed appropriate diameter and good dispersibility and DNR was loaded into CdTes with high encapsulation efficiency and drug loading. The maximum drug loading and encapsulation efficiency were 42.08 ± 0.64% and 74.52 ± 1.81%, respectively, at DNR concentration of 0.2mg/mL and anti-CD123 mAbs volume of 5ul (100ug/mL). Flow cytometry (FCM) showed that CD123 antigen was highly expressed on MUTZ-1 cells, and its expression rate was 72.89 ± 10.67%. In vitro experiments showed that the inhibition rate and apoptosis rate of MUTZ-1 cells treated with DNR-CdTe-CD123 were higher than those in the other groups (P< 0.05). Compared with the other groups, the level of apoptosis-related protein (P53, cleaved caspase-9, Bax and cleaved caspase-3) were upregulated in DNR-CdTe-CD123 group (P< 0.05). In vivo experiments, DNR-CdTe-CD123 can effectively inhibit the tumor growth of MDS-bearing nude mice and reduce the side effects of DNR on myocardial cells.Conclusion: The system of DNR-CdTe-CD123 enhances the therapeutic effects and reduce the side effects of DNR, thus providing a novel platform for MDS treatment.Keywords: myelodysplastic syndrome, daunorubicin, CdTe, anti-CD123 monoclonal antibody, drug delivery system
format	article
author	Guo D Xu P Chen D Wang L Zhu Y Zuo Y Chen B
author_facet	Guo D Xu P Chen D Wang L Zhu Y Zuo Y Chen B
author_sort	Guo D
title	Daunorubicin-Loaded CdTe QDs Conjugated with Anti-CD123 mAbs: A Novel Delivery System for Myelodysplastic Syndromes Treatment
title_short	Daunorubicin-Loaded CdTe QDs Conjugated with Anti-CD123 mAbs: A Novel Delivery System for Myelodysplastic Syndromes Treatment
title_full	Daunorubicin-Loaded CdTe QDs Conjugated with Anti-CD123 mAbs: A Novel Delivery System for Myelodysplastic Syndromes Treatment
title_fullStr	Daunorubicin-Loaded CdTe QDs Conjugated with Anti-CD123 mAbs: A Novel Delivery System for Myelodysplastic Syndromes Treatment
title_full_unstemmed	Daunorubicin-Loaded CdTe QDs Conjugated with Anti-CD123 mAbs: A Novel Delivery System for Myelodysplastic Syndromes Treatment
title_sort	daunorubicin-loaded cdte qds conjugated with anti-cd123 mabs: a novel delivery system for myelodysplastic syndromes treatment
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/c92989a988ce4d08905da43b89726273
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Daunorubicin-Loaded CdTe QDs Conjugated with Anti-CD123 mAbs: A Novel Delivery System for Myelodysplastic Syndromes Treatment

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