Liposomes targeted via two different antibodies: Assay, B-cell binding and cytotoxicity

2005 
Abstract The selective toxicity of anticancer drugs can be improved with the use of antibody-targeted liposomes. We hypothesize that liposomes targeted via antibodies against two or more receptor populations will increase the apparent receptor density on the target cells, resulting in improved therapeutic affects. A fluorescent assay was developed, using the fluorophores Alexa Fluor® 350 and 532 to label monoclonal antibodies (mAb), and used to quantitate two different mAb populations coupled to the same liposome surface to within ±10% of the values obtained with radiolabeled antibody ( 125 I) tracers. The binding and uptake of targeted liposomes by B lymphoma (Namalwa) cells were examined for either individual populations of αCD19-targeted or αCD20-targeted liposomes, mixed populations (1:1) of αCD19-targeted liposomes plus αCD20-targeted liposomes, and dual-targeted liposomes, i.e., equal amount of both αCD19 and αCD20 on the same liposomes. At similar antibody densities, the binding and uptake of the dual-targeted liposomes were greater than that of either individually targeted liposomes alone, and showed additivity. At the same total lipid and antibody densities, 1:1 mixtures of individually targeted liposomes gave similar results to dual-targeted liposomes. Cytotoxicity was also improved, with DXR-loaded dual-targeted liposomes appearing to have higher cytotoxicity than 1:1 mixtures of individually targeted liposomes.
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