title: Penetration of endothelial cell coated multicellular tumor spheroids by iron oxide nanoparticles.
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.
authors.affiliation: 1. Department of Chemistry, Brown University, Providence, RI 02912.
authors.forename: Don N
authors.initials: DN
authors.lastname: Ho
authors.forename: Nathan
authors.initials: N
authors.lastname: Kohler
authors.forename: Aruna
authors.initials: A
authors.lastname: Sigdel
authors.forename: Raghu
authors.initials: R
authors.lastname: Kalluri
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Morgan
authors.forename: Chenjie
authors.initials: C
authors.lastname: Xu
authors.forename: Shouheng
authors.initials: S
authors.lastname: Sun