Abstract
Abstract Background: Magnetic nanoparticles (MNPs) with theranostic features (diagnosis and treatment) have attracted significant attention and will greatly improve the scope of nanomedicine in cancer applications. The aim of this study is to develop a novel MNPs formulation composed of an iron oxide core coated with α-cyclodextrin and pluronic polymer (F68), to load an anti-cancer drug (curcumin, CUR) and prevent particle aggregation, respectively. The therapeutic efficacy and imaging capabilities of this novel formulation were evaluated in breast cancer cell line models. Methods: The physico-chemical analyses of curcumin loaded MNPs (MNP-CUR) were performed using dynamic light scattering (DLS), transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) analyses. MNP-CUR internalization was evaluated after 6 hrs incubation with MDA-MB-231 cancer cells by Prussian blue stain and TEM. Anti-cancer effects of the MNP-CUR formulation was determined by a tetrazolium based dye (MTT) and colony formation assays using “triple negative” MDA-MB-231 cancer cells. Tetramethylrhodamine, ethyl ester, perchlorate (TMRE), red mitochondrial superoxide indicator (Mitosox), and propidium iodide stains were used to evaluate the loss of mitochondrial membrane potential, reactive oxygen species (ROS) generation, and apoptosis/dead cells, respectively, to determine effects MNP-CUR on these cellular features. The imaging capability of this MNP-CUR formulation was analyzed using a magnetic resonance imaging (MRI) system. The magnetic targeting feature of the MNP-CUR formulation was evaluated using fluorescence microscopy. Results: We prepared MNP-CUR with an average aggregative particles size of ∼ 150 nm (individual particle grain size, ∼ 9-11 nm). Prussian blue stain data represent a preferential uptake of MNP-CUR in MDA-MB-231 cells in a dose dependant manner. TEM analysis demonstrates that accumulation of MNP-CUR nanoparticles in cancer cells indicate that particles are not attached on the surface of cells but internalized within the cells. The MNP-CUR formulation showed strong anti-cancer effects in breast cancer cells including “triple negative” MDA-MB-231 cancer cells compared to free curcumin. This formulation also enhanced loss of mitochondrial membrane potential, generation of ROS and apoptosis compared to free curcumin treatment. Additionally, the MNP-CUR formulation exhibits superior T2 imaging characteristics compared to T1. A significant increase of the targeting feature was observed with MNP-CUR in breast cancer cells. Conclusion: These data suggest that our novel MNP-CUR formulation exhibits potent anti-cancer activity along with imaging and magnetic targeting capabilities. This approach can be extended to pre-clinical and clinical use and may have importance in cancer treatment and cancer imaging in the future. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2893. doi:1538-7445.AM2012-2893
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