Drug Delivery | |
Anti-CD123 antibody-modified niosomes for targeted delivery of daunorubicin against acute myeloid leukemia | |
Hui Li1  Hui Jin2  Yin Wang2  Sheng-jun Mao2  Qiantao Wang2  Fu-rong Liu2  Ming Li2  Chen Chen2  | |
[1] Department of Hematology, Sichuan Academy of Medical Sciences and Sichuan Provincial People Hospital, Chengdu, Chin;Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education and West China School of Pharmacy, Sichuan University, Chengdu, China; | |
关键词: Niosome; CD123; drug targeting; acute myeloid leukemia; daunorubicin; | |
DOI : 10.1080/10717544.2017.1333170 | |
来源: Taylor & Francis | |
【 摘 要 】
A novel niosomal delivery system was designed and investigated for the targeted delivery of daunorubicin (DNR) against acute myeloid leukemia (AML). Anti-CD123 antibodies conjugated to Mal-PEG2000-DSPE were incorporated into normal niosomes (NS) via a post insertion method to afford antibody-modified niosomes (CD123-NS). Next, NS was modified with varying densities of antibody (0.5 or 2%, antibody/Span 80, molar ratio), thus providing L-CD123-NS and H-CD123-NS. We studied the effect of antibody density on the uptake efficiency of niosomes in NB4 and THP-1 cells, on which CD123 express differently. Our results demonstrate CD123-NS showed significantly higher uptake efficiency than NS in AML cells, and the uptake efficiency of CD123-NS has been ligand density-dependent. Also, AML cells preincubated with anti-CD123 antibody showed significantly reduced cellular uptake of CD123-NS compared to control. Further study on the uptake mechanism confirmed a receptor-mediated endocytic process. Daunorubicin (DNR)-loaded H-CD123-NS demonstrated a 2.45- and 3.22-fold higher cytotoxicity, compared to DNR-loaded NS in NB4 and THP-1 cells, respectively. Prolonged survival time were observed in leukemic mice treated with DNR-H-CD123-NS. Collectively, these findings support that the CD123-NS represent a promising delivery system for the treatment of AML.
【 授权许可】
CC BY
【 预 览 】
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RO202201011968957ZK.pdf | 1222KB | download |