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Cancer Nanotechnology Platform Partnerships

Nanotechnology Platform for Pediatric Brain Cancer Imaging and Therapy

Principal Investigator: Miqin Zhang, Ph.D.

University of Washington

The long-term objective of this application is to help eliminate the suffering and death of children with brain cancer. Brain cancers are the most common solid tumors in children. Survival remains poor for patients with metastases or recurrence; current therapy commonly causes severe neurocognitive deficits. The leading institutions include the University of Washington (UW), the Fred Hutchinson Cancer Research Center (FHCRC), Children's Hospital & Regional Medical Center (CHRMC), Children's National Medical Center (CNMC) and Philips Medical Systems (PMS). Our multidisciplinary approach includes expertise in Materials Science (Miqin Zhang, Principle Investigator, UW, nanoparticle synthesis, ligand conjugation and in vitro studies), Molecular Tumor Biology (James Olson, FHCRC, UW, CHRMC, in vivo models of pediatric brain cancer), Clinical Radiology (Raymond Sze, CNMC), MR Imaging Physics (Donghoon Lee, UW and Stefan Fischer, PMS, small animal coil design, MR imaging, and signal quantification), and Neurological Surgery (Richard Ellenbogen, UW, CHRMC), brain tumor surgery and translation of basic research to clinical trials). The Specific Aims (Cancer Focus Areas) are: Aim 1 (Reporters of therapeutic efficacy): develop a tumor-targeting dual MR and optical nanoparticulate contrast agent that will enable presurgical planning and intraoperative delineation of tumor margins; Aim 2 (Multifunctional therapeutics): develop a tumor-targeted dual MR and optical nanoparticulate imaging agent carrying a chemotherapeutic payload. Following synthesis of the multifunctional nanoparticles, targeting specificity, contrast agent dose, timing of scanning, image contrast, and therapeutic efficacy will be optimized progressively in vitro then in flank xenograft and spontaneous intracranial mouse models of pediatric brain cancer. Public health relevance: the tumor targeting nanoparticle agents proposed may enable dramatically improved diagnosis and treatment for children with brain cancer while concurrently reducing the frequently severe complications resulting from current treatment-related toxicities.

Publications

N. Kohler, C. Sun, A. Fichtenholtz, J. Gunn, C. Fang, and M. Zhang* "Methotrexate Immobilized Poly(ethylene glycol) Magnetic Nanoparticles for MR Imaging and Drug Delivery", Small 2 (6), 785-791 (2006).

C. Sun, R. Sze, and M. Zhang "Folate acid-PEG conjugated superparamagnetic nanoparticles for targeted cellular uptake and detection by MRI", Journal of Biomedical Materials Research, 78(3):550-7 (2006).

O. Veiseh, C. Sun, J. Gunn, N. Kohler, P. Gabikian, D.Lee, N. Bhattarai, R.Ellenbogen, R. Sze, A. Hallahan, J. Olson, and M. Zhang "An optical and MRI multifunctional nanoprobe for targeting gliomas”, Nano Letters, 5 (6), 1003-1008 (2005).

N. Kohler, C. Sun, J. Wang, and M. Zhang "Methotrexate-modified superparamagnetic nanoparticles and their intracellular uptake into human cancer cells”, Langmuir, 21 (19), 8858-8864 (2005).