Journal
NEUROSURGERY
Volume 64, Issue 5, Pages 965-971Publisher
OXFORD UNIV PRESS INC
DOI: 10.1227/01.NEU.0000344150.81021.AA
Keywords
Brain tumor; Nanoparticle; Tumor imaging
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Funding
- National Institute of Biomedical Imaging and Bioengineering [1R01EB007977-01]
- National Cancer Institute [1R21CA125297-01A1, IF32CA726295-01A1]
- Congress of Neurological Surgeons Basic /Translational Resident Research Fellowship
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OBJECTIVE: To synthesize and complete in vitro characterization of a novel, tumor-targeted nanodevice for visible intraoperative delineation of brain tumors. METHODS: The 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. RESULTS: Incubation 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. CONCLUSION: F3-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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