Abstract 4298: Nanomagnetic levitation based 3-D cultures of breast and colon cancer cells for high throughput drug screening and xenograft studies
Authors: Harvey L. Bumpers, Janagama D. Goud, Wayne L. DeBeatham, Upender Manne
Journal: Cancer Research (2011)

Abstract Introduction. Drug discovery and development, disease models, and drug testing in various cell-based platforms demands a highly in vivo-like microenvironments for In Vitro applications. Advancement in cell culture methods from 2-D to 3-D is a big leap by demonstrating significant differences in cellular characteristics and behavior enabling the assessment of drug efficacy, pharmacokinetics and pharmacodynamics. However, use of 3-D scaffold materials such as standard (1%) hydro gel acts as a transport barrier within the tissue construct and impedes drug delivery to target cells. Thus nutrients are limited and metabolic waste accumulates in the gel. Description of Procedure. To overcome these problems, we developed breast cancer (MDA-MB-231, MDA-MB-468) and colon carcinoma (HT-29, WiDr, SW 480) cell cultures by nanomagnetic levitation using carbon encapsulated cobalt magnetic nanomaterial(&amp;lt;50 nm particle size; resistivity 6.24 μΩ-cm, 20°C) to mimic in vivo cellular conditions for efficient drug delivery. The poor oxidation resistance of the bare metal magnetic nanoparticles were carbon coated (approximately three graphitic layers used) to make these magnetic particles biocompatible and stable as intracellular entities. The cancer cells were suspended in the dilute (0.25%) hydro gel mixed with carbon encapsulated cobalt magnetic nanomaterial and allowed to incubate overnight. The dilute hydrogel matrix prevents aggregation of the magnetic nanoparticles. The cells with internalized magnetic nanoparticles were then separated from the gel and grown in supplemented RPMI culture medium. The cell colonies grew in suspension under magnetic influence. Cell colonies viability was established using ethidium bromide and acridine stain. Summary. The cell colonies have been maintained as in vitro 3D-tumor masses for more than a month. Nanomagnetic levitation may serve as replacement for those 3-D cultures grown in hydogel. These 3-D cell cultures underwent apoptosis when exposed to nefM1 apoptotic peptides and may represent an alternative to the use of animal models for initial testing of drug therapy on tumor masses. Furthermore, the nanomagnetic levitation system may be a better construct for 3-D cell cultures than hydro gel alone which has served as a standard. The efficiency of developing in vivo xenografts from these 3-D cultures is being evaluated in the SCID mouse. Conclusion. The novelty of this research is in using, for the first time, the carbon encapsulated magnetic nanoparticles for stability and biocompatibility to create 3-D in vitro cancer cell colonies to mimic in vivo xenografts. This technical strategy can be applied to any cell or tissue type. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4298. doi:10.1158/1538-7445.AM2011-4298