Nathan Kohler PhD, Presenter: Nothing to Disclose

Chenjie Xu BS, Abstract Co-Author: Nothing to Disclose

Jin Xie BS, Abstract Co-Author: Nothing to Disclose

Don Ho BS, Abstract Co-Author: Nothing to Disclose

Jeffrey Morgan PhD, Abstract Co-Author: Nothing to Disclose

Raghu Kalluri PhD, Abstract Co-Author: Nothing to Disclose

Shouheng Sun PhD, Abstract Co-Author: Nothing to Disclose

et al, Abstract Co-Author: Nothing to Disclose

et al, Abstract Co-Author: Nothing to Disclose

To develop a multifunctional nanoparticulate system as MRI contrast agents for angiogenic tumor imaging and anti-angiogenic therapy.

10 nm Fe3O4 nanoparticles were prepared by reductive decomposition of iron acetylacetonate in the presence of oleic acid and oleylamine. The as synthesized nanoparticles were further functionalized with dopamine and a 3000 MW poly(ethylene glycol) linker which was coupled to tumstatin, a low molecular weight peptide specific for the αVβIII integrin expressed on the surface of endothelial cells. The hydrodynamic size of the tumstatin nanoparticles were measured by dynamic light scattering analysis. The stability of the nanoparticles was tested in phosphate buffered saline + 10% fetal bovine serum. Reduction in CPAE (endothelial cell) viability was tested in vitro through WST-1 assay analysis. Tumstatin nanoparticle uptake was quantified through Inductively Coupled Plasmon-Atomic Emission Spectroscopy (ICP-AES). Visualization of nanoparticle uptake was demonstrated through scanning confocal microscopy. T2 MRI contrast enhancement was tested using a Siemens Trio 3T scanner.

DLS analysis demonstrated nanoparticle stability of 24 hours in simulated human plasma. In vitro cell culture with tumstatin conjugated nanoparticles demonstrated an 80% mean reduction in cellular viability of CPAE cells compared to the control without tumstatin, and a 29% reduction in cell viability compared to free tumstatin control. Nanoparticle uptake showed up to 3.03E-3 ng/cell iron through ICP-AES analysis. Scanning confocal microscopy of tumstatin nanoparticles demonstrated particle uptake within the cellular cytoplasm. Individual particle uptake in CPAE cells was visualized with TEM. MRI phantom imaging of tumstatin nanoparticles showed an R2* of 22.11 and R2 of 2.443 (1/s)/(ug/mL).

Tumstatin modified iron oxide nanoparticles targeted for endothelial cells induced a reduction of cellular viability by 80% and T2 MRI contrast enhancement.

The peptide-Fe3O4 nanoparticle system may be used for vascular contrast enhancement in angiogenic tumors.

Kohler, N, Xu, C, Xie, J, Ho, D, Morgan, J, Kalluri, R, Sun, S, et al, , et al, , Tumstatin Conjugated Iron Oxide Nanoparticles for MRI Contrast-enhancement and Anti-angiogenic Drug Therapy.  Radiological Society of North America 2007 Scientific Assembly and Annual Meeting, November 25 - November 30, 2007 ,Chicago IL. http://archive.rsna.org/2007/5003396.html