Jie Zhang, Shishou Kang School of Physics, Shandong University, Jinan 250100, P.R. China

1. Magnetic Nanoparticles Tailored for a Multifunctional Nanoplatform for Cancer Targeting, Imaging, and Therapy Magnetite Nanoparticle Synthesis Motivation and Purpose A Multifunctional Nanoplatform for Cancer Targeting, Imaging, Therapy Imagine a multifunctional nanoplatform with the ability to specifically target cancerous cells, enhance the contrast for MRI imaging, and effect selective magnetic triggering of cancer therapy, either hyperthermia therapy or controlled release of a cancer drug. The nanoplatform consists of a non-replicative human adenovirus, genetically engineered to target specific cancer cells. Chemically linked to the adenovirus are different magnetic nanoparticles and polymer beads, each tailored for a specific function. One type of magnetic particle will be of the optimum size and magnetic properties to provide contrast enhancement for sensitive MRI, allowing an unprecedented ability to image the cancer tissue. Another type of nanoparticle will be tailored to absorb a specific ac frequency magnetic field (radio frequency, rf) and efficiently generate heat which kills the cancerous tissue-a magnetically triggered hyperthermia therapy. The polymeric beads contain different magnetic nanoparticles and a cancer therapeutic agent trapped in a thermally responsive, controlled release polymer. Irradiation with a different rf ac magnetic field will heat the magnetic particles, thereby heating the polymer matrix above a temperature where it swells, allowing the cancer therapies by an external magnetic field. Here we pursue a basic research project aimed at demonstrating the materials science that would enable such a nanoplatform. 4nm Fe3O4 dispersed in Hexane (2 mmol) Fe(acac)3+ (20 mL) phenyl ether + (10 mmol)1,2- hexadecanediol+(6 mmol) Oleic Acid + (6 mmol) Oleylamine Heated under N2 to reflux 4nm Fe3O4 dispersed in H2O (20 mL) 2-phrrolidone + (2 mmol) Fe(acac)3 Heated under N2 reflux for 10 min 6nm Fe3O4 dispersed in Hexane (2 mmol) Fe(acac)3+(10 mmol)1,2- hexadecanediol+(6mmol)Oleic Acid+ (6mmol)Oleylamine+(20mL) benzyl ether Heated under N2 at 200℃ for 2 hours, then heated to reflux for 1 hour 11nmγ-Fe2O3 dispersed in Hexane (3.04 mmol) Fe(CO)5 was injected into a mixture of (20mL) octyl ether +(6.08 mmol) oleic aced at 100℃. Then, it was slowly heated under N2 to reflux Jie Zhang, Shishou Kang School of Physics, Shandong University, Jinan 250100, P.R. China Fig 1. A multifunctional nanoplatform for cancer targeting, imaging and therapy, consisting of an adenovirus labeled with c nanoparticles. Fig 5. 6nm Fe3O4 in Hexane Fig 4. 4nm Fe3O4 in Hexane Fig 2. Linking group for binding the magnetite particles to the adenovirus. The silane group will react with surface hydroxide groups to make a covalent bong with the particles. The biotin group will bind to biotin receptors on the surface of the adenovirus. Fig7. 11nmγ-Fe2O3 in Hexane Fig 6. 4nm Fe3O4 in H2O • Our Plans • Make larger particles • Make cobalt ferrite and manganese ferrite nanoparticles • A complete magnetic characterization of the particles Initial susceptibility Saturation magnetization Anisotropy • Attach linking groups and bind the particles to human adenovirus • Find the best means making the particles water dispersible Fig 3. Magnetic fluid localized to the cancerous tissue. Alternating magnetic field heats magnetic particles (typically ~45-55ºC), and ablates cancerous tissue.