Background:The next generation magnetic nanoparticles (MNPs) with theranostic applications have attracted significant attention and will greatly improve nanomedicine in cancer therapeutics. Such novel MNP formulations must have ultra-low particle size, high inherent magnetic properties, effective imaging, drug targeting, and drug delivery properties. To achieve these characteristic properties, a curcumin-loaded MNP (MNP-CUR) formulation was developed. Methods: MNPs were prepared by chemical precipitation method and loaded with curcumin (CUR) using diffusion method. The physicochemical properties of MNP-CUR were characterized using dynamic light scattering, transmission electron microscopy, and spectroscopy. The internalization of MNP-CUR was achieved after 6 hours incubation with MDA-MB-231 breast cancer cells. The anticancer potential was evaluated by a tetrazolium-based dye and colony formation assays. Further, to prove MNP-CUR results in superior therapeutic effects over CUR, the mitochondrial membrane potential integrity and reactive oxygen species generation were determined. Magnetic resonance imaging capability and magnetic targeting property were also evaluated. Results: MNP-CUR exhibited individual particle grain size of ∼9 nm and hydrodynamic average aggregative particle size of ∼123 nm. Internalized MNP-CUR showed a preferential uptake in MDA-MB-231 cells in a concentration-dependent manner and demonstrated accumulation throughout the cell, which indicates that particles are not attached on the cell surface but internalized through endocytosis. MNP-CUR displayed strong anticancer properties compared to free CUR. MNP-CUR also amplified loss of potential integrity and generation of reactive oxygen species upon treatment compared to free CUR. Furthermore, MNP-CUR exhibited superior magnetic resonance imaging characteristics and significantly increased the targeting capability of CUR. Conclusion: MNP-CUR exhibits potent anticancer activity along with imaging and magnetic targeting capabilities. This approach can be extended to preclinical and clinical use and may have importance in cancer treatment and cancer imaging in the future. Further, if these nanoparticles can functionalize with antibody/ligands, they will serve as novel platforms for multiple biomedical applications.

Ovarian cancer continues to be a leading cause of cancer related deaths for women. Anticancer agents effective against chemo-resistant cells are greatly needed for ovarian cancer treatment. Repurposing drugs currently in human use is an attractive strategy for developing novel cancer treatments with expedited translation into clinical trials. Therefore, we examined whether ormeloxifene (ORM), a non-steroidal Selective Estrogen Receptor Modulator (SERM) currently used for contraception, is therapeutically effective at inhibiting ovarian cancer growth. We report that ORM treatment inhibits cell growth and induces apoptosis in ovarian cancer cell lines, including cell lines resistant to cisplatin. Furthermore, ORM treatment decreases Akt phosphorylation, increases p53 phosphorylation, and modulates the expression and localization patterns of p27, cyclin E, cyclin D1, and CDK2. In a pre-clinical xenograft mouse ORM treatment significantly reduces tumorigenesis and metastasis. These results indicate that ORM effectively inhibits the growth of cisplatin resistant ovarian cancer cells. ORM is currently in human use and has an established record of patient safety. Our encouraging in vitro and pre-clinical in vivo findings indicate that ORM is a promising candidate for the treatment of ovarian cancer.

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

The goal of this project was to develop a lowercost medium for nisin production, so this bacteriocin could be used in a broader range of industrial fermentation processes. The objectives included: (1) evaluating methods for controlling the inhibitory effect of lactic acid produced during fermentation, and (2) comparing two inexpensive complex media for nisin production. Lactococcus lactis subsp. lactis was cultured in shake flasks on LaurelTryptose broth to evaluate a range of buffers for pH control. NaHCO 3 proved to be an effective buffer for increasing nisin production. Subsequent trials then evaluated condensed corn soluble (CCS, a fuel ethanol production byproduct) and cheese whey as inexpensive growth media. CCS was shown to be an efficient, low-cost medium for high nisin titers and yields. These modifications reduced the medium costs for nisin production from $600/ kg nisin (based on Laurel-Tryptose broth medium) to $35-40/kg nisin for the corn solubles medium.