Daunorubicin-Loaded CdTe QDs Conjugated with Anti-CDI23 mAbs: A Novel Delivery System for Myelodysplastic Syndromes Treatment

Introduction: 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. Howeve...

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Bibliographic Details
Published in:International journal of nanomedicine 2020-01, Vol.15, p.521
Main Authors: Guo, Dan, Xu, Peipei, Chen, Dangui, Wang, Lili, Zhu, Yudi, Zuo, Yifan, Chen, Bing
Format: Article
Language:English
Subjects:
Acute myelocytic leukemia
Anthracyclines
Antibodies
Antigens
Biological products
Bonds (Securities)
Cancer
Cancer treatment
Characterization
Chemotherapy
Daunorubicin
Drug delivery systems
Health aspects
Monoclonal antibodies
Myelodysplastic syndromes
Myeloid leukemia
Novels
Toxicity
Tumor proteins
Tumors
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Summary:Introduction: 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 [+ or -] 0.64% and 74.52 [+ or -] 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 [+ or -] 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
ISSN:1178-2013
DOI:10.2147/IJN.S233395