Anti-CD123 antibody-modified niosomes for targeted delivery of daunorubicin against acute myeloid leukemia

• Published in: Drug delivery Vol. 24; no. 1; pp. 882 - 890
• Main Authors: Liu, Fu-rong, Jin, Hui, Wang, Yin, Chen, Chen, Li, Ming, Mao, Sheng-jun, Wang, Qiantao, Li, Hui
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 2017; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: acute myeloid leukemia; Animals; Cancer therapies; CD123; Cell cycle; Cell Line, Tumor; Daunorubicin; Drug delivery systems; drug targeting; Drug therapy; Efficiency; Hematology; Immunoglobulins; Interleukin-3 Receptor alpha Subunit; Laboratories; Leukemia; Leukemia, Myeloid, Acute; Liposomes; Medical prognosis; Mice; Niosome; Pharmacy; Stem cells; Surfactants; drug targeting; acute myeloid leukemia; Niosome; CD123; daunorubicin
• ISSN: 1071-7544; 1521-0464
• DOI: 10.1080/10717544.2017.1333170

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-PEG 2000 -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.