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Specific Targeting of Brain Tumors with an Optical/Magnetic Resonance Imaging Nanoprobe across the Blood-Brain Barrier

Departments of ¹ Materials Science and Engineering, ² Radiology, ³ Bioengineering, and ⁴ Neurological Surgery, University of Washington; ⁵ Clinical Research Division, Fred Hutchinson Cancer Research Center; and ⁶ Seattle Children's Hospital and Regional Medical Center, Seattle, Washington

Requests for reprints: Miqin Zhang, Department of Materials Science and Engineering, University of Washington, Box 352120, 302L Roberts, Seattle, WA 99195. Phone: 206-616-9356; Fax: 206-543-3100; E-mail: mzhang{at}u.washington.edu.

Key Words: nanoparticle • brain tumor • MRI • targeting • blood-brain barrier

Nanoparticle-based platforms have drawn considerable attention for their potential effect on oncology and other biomedical fields. However, their in vivo application is challenged by insufficient accumulation and retention within tumors due to limited specificity to the target, and an inability to traverse biological barriers. Here, we present a nanoprobe that shows an ability to cross the blood-brain barrier and specifically target brain tumors in a genetically engineered mouse model, as established through in vivo magnetic resonance and biophotonic imaging, and histologic and biodistribution analyses. The nanoprobe is comprised of an iron oxide nanoparticle coated with biocompatible polyethylene glycol–grafted chitosan copolymer, to which a tumor-targeting agent, chlorotoxin, and a near-IR fluorophore are conjugated. The nanoprobe shows an innocuous toxicity profile and sustained retention in tumors. With the versatile affinity of the targeting ligand and the flexible conjugation chemistry for alternative diagnostic and therapeutic agents, this nanoparticle platform can be potentially used for the diagnosis and treatment of a variety of tumor types. [Cancer Res 2009;69(15):6200–7]