Plasmon resonance coupling of metal nanoparticles for molecular imaging of carcinogenesis in vivo.
An effective cancer control strategy requires improved early detection methods, patient-specific drug selection, and the ability to assess response to targeted therapeutics. Recently, plasmon resonance coupling between closely spaced metal nanoparticles has been used to develop ultrasensitive bioanalytical assays in vitro. We demonstrate the first in vivo application of plasmon coupling for molecular imaging of carcinogenesis. We describe molecular-specific gold bioconjugates to image epidermal growth factor receptor (EGFR); these conjugates can be delivered topically and imaged noninvasively in real time. We show that labeling with gold bioconjugates gives information on the overexpression and nanoscale spatial relationship of EGF receptors in cell membranes, both of which are altered in neoplasia. EGFR-mediated aggregation of gold nanoparticles in neoplastic cells results in more than a 100-nm color shift and a contrast ratio of more than tenfold in images of normal and precancerous epithelium in vivo, dramatically increasing contrast beyond values reported previously for antibody-targeted fluorescent dyes.
Aaron
Jesse
J
University of Texas at Austin, Department of Biomedical Engineering, Austin, Texas 78712, USA.
Nitin
Nitin
N
Travis
Kort
K
Kumar
Sonia
S
Collier
Tom
T
Park
Sun Young
SY
José-Yacamán
Miguel
M
Coghlan
Lezlee
L
Follen
Michele
M
Richards-Kortum
Rebecca
R
Sokolov
Konstantin
K
D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D045744:Cell Line, Tumor; D006224:Cricetinae; D066246:ErbB Receptors / Q000032:analysis* / Q000737:chemistry; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008647:Mesocricetus; D015336:Molecular Probe Techniques; D053758:Nanoparticles / Q000737:chemistry*; D009363:Neoplasm Proteins / Q000032:analysis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020349:Surface Plasmon Resonance / Q000379:methods*
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D006046:Gold; D066246:ErbB Receptors