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Theranostics 2012; 2(1):66-75. doi:10.7150/thno.3568 This issue Cite

Research Paper

Penetration of Endothelial Cell Coated Multicellular Tumor Spheroids by Iron Oxide Nanoparticles

Don N. Ho^1,2, Nathan Kohler¹, Aruna Sigdel¹, Raghu Kalluri³, Jeffrey R. Morgan^2✉, Chenjie Xu^1,4✉, Shouheng Sun^1✉

1. Department of Chemistry, Brown University, Providence, RI 02912
2. Center of Biomedical Engineering, Brown University, Providence, RI 02912;
3. Department of Biological Chemistry and Molecular Pharmacology, Harvard-MIT Division of Health Sciences and Technology, Department of Medicine Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02114, USA
4. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard Stem Cell Institute, Harvard-MIT, Division of Health Sciences and Technology, 65 Landsdowne Street, Cambridge, MA 02139, USA

✉ Corresponding author: Email: Jeffrey_Morganedu; chjxuedu; ssunedu

Abstract

Iron oxide nanoparticles are a useful diagnostic contrast agent and have great potential for therapeutic applications. Multiple emerging diagnostic and therapeutic applications and the numerous versatile parameters of the nanoparticle platform require a robust biological model for characterization and assessment. Here we investigate the use of iron oxide nanoparticles that target tumor vasculature, via the tumstatin peptide, in a novel three-dimensional tissue culture model. The developed tissue culture model more closely mimics the in vivo environment with a leaky endothelium coating around a glioma tumor mass. Tumstatin-iron oxide nanoparticles showed penetration and selective targeting to endothelial cell coating on the tumor in the three-dimensional model, and had approximately 2 times greater uptake in vitro and 2.7 times tumor neo-vascularization inhibition. Tumstatin provides targeting and therapeutic capabilities to the iron oxide nanoparticle diagnostic contrast agent platform. And the novel endothelial cell-coated tumor model provides an in vitro microtissue environment to evaluate nanoparticles without moving into costly and time-consuming animal models.

Keywords: iron oxide nanoparticles, tumstatin, tumor penetration, multicellular tumor spheroids, theranostic, magnetic, nanoparticle, imaging, drug delivery, anti-angiogenesis

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