398661 Anti-CD123 Antibody Labelled Polymer Micelles Target Leukemia Cells

Monday, November 17, 2014
Galleria Exhibit Hall (Hilton Atlanta)
Steven Tau1, Michael Baranello1, Danielle Benoit2 and David Foster1, (1)Chemical Engineering, University of Rochester, Rochester, NY, (2)Department of Biomedical Engineering, University of Rochester, Rochester, NY

Self-assembled polymer micelles have been shown to be effective vehicles to transport hydrophobic anticancer drugs. Micelles composed of poly(styrene-alt-maleic anhydride)-b-poly(styrene) (PSMA-b-PS) have been shown to display aqueous stability, drug loading, and functionalization. Interleukin-3 receptor alpha chain (CD123) is specifically expressed in many hematological malignancies, including acute myeloid leukemia (AML). Therefore, anti-CD123 antibody was conjugated to (PSMA-b-PS) micelles in order to fabricate nanoparticles that target cells with CD123 expression. Two methods were used and evaluated in linking the antibody to micelles. Conjugates were formed via carbodiimide crosslinking reagents or Copper(I)-Catalyzed Azide-Alkyne Cycloaddition, a type of “click chemistry”. The antibody concentration was quantified with fluoraldehyde (OPA) assay, and conjugation efficiencies of 20.1% and 16.4% were found for carbodiimide and click reactions respectively. Antibodies retained immunoreactivity post conjugation. Micelles were fluorescently labeled post conjugation for in vitro studies. Interactions between antibody-conjugated micelles and a CD123 expressing leukemia cell (MV-4-11) were assessed with flow cytometry. It was found that anti-CD123 conjugated micelles effectively bound to MV-4-11 cells with a 5-fold increase in cellular fluorescence compared to untargeted micelles. Our results suggest that anti-CD123 micelles serve as a useful targeted vehicle for delivery of AML therapies.

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