In vitro characterization of a targeted, dye-loaded nanodevice for intraoperative tumor delineation.
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.


CONCLUSIONS
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.
Orringer
Daniel A
DA
Department of Neurosurgery, University of Michigan Health System, Ann Arbor, Michigan 48109-5338, USA.
Koo
Yong-Eun L
YE
Chen
Thomas
T
Kim
Gwangseong
G
Hah
Hoe Jin
HJ
Xu
Hao
H
Wang
Shouyan
S
Keep
Richard
R
Philbert
Martin A
MA
Kopelman
Raoul
R
Sagher
Oren
O
D000180:Acrylic Resins / Q000008:administration & dosage* / Q000378:metabolism; D045744:Cell Line, Tumor; D003124:Colorimetry / Q000379:methods; D004305:Dose-Response Relationship, Drug; D000939:Epitopes; D005456:Fluorescent Dyes; D005910:Glioma / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning / Q000379:methods; D053758:Nanoparticles / Q000008:administration & dosage*; D010750:Phosphoproteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D000097796:Nucleolin; D000099166:Polyacrylamides
D000180:Acrylic Resins; D000939:Epitopes; D005456:Fluorescent Dyes; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin; D000099166:Polyacrylamides; C455179:F3 epitope