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), and Philips Medical Systems (PMS). Our multidisciplinary approach includes expertise in Materials Science (Miqin Zhang (UW), Lead Investigator for iron oxide nanoparticle synthesis for tumor targeting, imaging, and treatment); molecular tumor biology (James Olson (FHCRC, UW, CHRMC), Lead Investigator for in vitro and in vivo models of pediatric brain cancer); MR imaging physics (Donghoon Lee (UW) and Stefan Fischer (PMS), Lead Investigators for optimization of small animal coil design, pulse sequences, and signal quantification); and clinical and small animal diagnostic imaging interpretation (Raymond Sze (UW, CHRMC), Principal Investigator).
The Specific Aims (and 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 dose, timing of scanning, image contrast, and therapeutic efficacy will be optimized progressively in in vitro then in vivo 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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA119408-02
Application #
7127681
Study Section
Special Emphasis Panel (ZCA1-SRRB-C (O1))
Program Officer
Grodzinski, Piotr
Project Start
2005-09-30
Project End
2009-07-31
Budget Start
2006-09-01
Budget End
2007-07-31
Support Year
2
Fiscal Year
2006
Total Cost
$323,770
Indirect Cost
Name
University of Washington
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Wang, Kui; Park, James O; Zhang, Miqin (2013) Treatment of glioblastoma multiforme using a combination of small interfering RNA targeting epidermal growth factor receptor and *-catenin. J Gene Med 15:42-50
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Stroud, Mark R; Hansen, Stacey J; Olson, James M (2011) In vivo bio-imaging using chlorotoxin-based conjugates. Curr Pharm Des 17:4362-71
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Kievit, Forrest M; Wang, Freddy Y; Fang, Chen et al. (2011) Doxorubicin loaded iron oxide nanoparticles overcome multidrug resistance in cancer in vitro. J Control Release 152:76-83
Park, James O; Stephen, Zachary; Sun, Conroy et al. (2011) Glypican-3 targeting of liver cancer cells using multifunctional nanoparticles. Mol Imaging 10:69-77
Veiseh, Omid; Gunn, Jonathan W; Zhang, Miqin (2010) Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. Adv Drug Deliv Rev 62:284-304
Lee, Michelle Jeung-Eun; Veiseh, Omid; Bhattarai, Narayan et al. (2010) Rapid pharmacokinetic and biodistribution studies using cholorotoxin-conjugated iron oxide nanoparticles: a novel non-radioactive method. PLoS One 5:e9536
Kievit, Forrest M; Veiseh, Omid; Fang, Chen et al. (2010) Chlorotoxin labeled magnetic nanovectors for targeted gene delivery to glioma. ACS Nano 4:4587-94
Kievit, Forrest M; Florczyk, Stephen J; Leung, Matthew C et al. (2010) Chitosan-alginate 3D scaffolds as a mimic of the glioma tumor microenvironment. Biomaterials 31:5903-10

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