Abstract 5514: Targeted liposomes in cancer therapy

Abstract

Abstract The purpose of this project was to design a liposomal formulation which targets the SLC transporter. Daunorubicin, an anticancer drug, used as a model was encapsulated in the targeted liposomal formulation and the cellular uptake and cytotoxicity of targeted liposomal daunorubicin (TLD) as well as the mechanisms of cellular uptake were evaluated using the A549 lung cancer cell line. A quantity of 3×105/2ml cells of A549 were cultured in each well of 6 well plates in RPMI medium. The cells were treated with TLD, non targeted liposomal (NTL) daunorubicin and free, non-encapsulated daunorubicin containing 10µM and 5µM drug. They were incubated for 5-6 hours at 37oC and analyzed using flow cytometry and fluorescence imaging. The cytotoxicity of the formulations was determined using MTS assay. The IC50 was determined from the growth inhibition curves of cell viability. Furthermore, the mechanism of internalization of the TLD formulation was studied using inhibitors specific to each pathway of internalization. The results show that the cellular uptake TLD showed a significant increase of 2- fold compared to that of NTL and free drug for both concentrations (10µM and 5µM). These results were also consistent with the cytotoxicity study showing higher cytotoxicity of TLD compared to NTL and free drug, The IC50 of TDL showed a 2.3-fold and 3.4-fold decrease compared to NTL and free drug, respectively. Also the data showed decrease in the cellular uptake of TLD when the macropinocytosis pathway was inhibited. Depletion of cholesterol in the cellular wall also reduced the cellular uptake of the TLD formulation. The results indicate that our novel targeted liposomal formulation shows enhanced cellular uptake and cytotoxicity likely due to macropinocytosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5514.