• Daniel A Orringer, Yong-Eun L Koo, Thomas Chen, Gwangseong Kim, Hoe Jin Hah, Hao Xu, Shouyan Wang, Richard Keep, Martin A Philbert, Raoul Kopelman, and Oren Sagher.
• Department of Neurosurgery, University of Michigan Health System, Ann Arbor, Michigan 48109-5338, USA.
• Neurosurgery. 2009 May 1; 64 (5): 965972965-71; discussion 971-2.

ObjectiveTo synthesize and complete in vitro characterization of a novel, tumor-targeted nanodevice for visible intraoperative delineation of brain tumors.MethodsThe ability of dye-loaded polyacrylamide nanoparticles (NP) containing methylene blue, Coomassie blue, or indocyanine green to cause color change in the 9L glioma cell lines was evaluated. Cells were incubated with dye-loaded NPs, photographed, and analyzed colorimetrically. Confocal microscopy was used to determine subcellular localization of NPs in treated cells.ResultsIncubation of glioma cell lines with dye-loaded NPs resulted in clearly visible, quantifiable cell tagging in a dose- and time-dependent manner. Dye-loaded NPs were observed to bind to the surface and become internalized by glioma cells. Coating the NP surface with F3, a peptide that binds to the tumor cell surface receptor nucleolin, significantly increased NP affinity for glioma cells. F3 targeting also significantly increased the rate of cell tagging by dye-loaded NPs. Finally, F3-targeted NPs demonstrated specificity for targeting various cancer cell lines based on their surface expression of cell surface nucleolin.ConclusionF3-targeted dye-loaded NPs efficiently cause definitive color change in glioma cells. This report represents the first use of targeted NPs to cause a visible color change in tumor cell lines. Similar nanodevices may be used in the future to enable visible intraoperative tumor delineation during tumor resection.

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