title: Quantification of the binding potential of cell-surface receptors in fresh excised specimens via dual-probe modeling of SERS nanoparticles.
abstract: The complete removal of cancerous tissue is a central aim of surgical oncology, but is difficult to achieve in certain cases, especially when the removal of surrounding normal tissues must be minimized. Therefore, when post-operative pathology identifies residual tumor at the surgical margins, re-excision surgeries are often necessary. An intraoperative approach for tumor-margin assessment, insensitive to nonspecific sources of molecular probe accumulation and contrast, is presented employing kinetic-modeling analysis of dual-probe staining using surface-enhanced Raman scattering nanoparticles (SERS NPs). Human glioma (U251) and epidermoid (A431) tumors were implanted subcutaneously in six athymic mice. Fresh resected tissues were stained with an equimolar mixture of epidermal growth factor receptor (EGFR)-targeted and untargeted SERS NPs. The binding potential (BP; proportional to receptor concentration) of EGFR - a cell-surface receptor associated with cancer - was estimated from kinetic modeling of targeted and untargeted NP concentrations in response to serial rinsing. EGFR BPs in healthy, U251, and A431 tissues were 0.06 ± 0.14, 1.13 ± 0.40, and 2.23 ± 0.86, respectively, which agree with flow-cytometry measurements and published reports. The ability of this approach to quantify the BP of cell-surface biomarkers in fresh tissues opens up an accurate new approach to analyze tumor margins intraoperatively.
authors.affiliation: 1] Biomedical Engineering, Illinois Institute of Technology, Chicago, IL 60616, USA [2] Electrical Engineering, Illinois Institute of Technology, Chicago, IL 60616, USA.
authors.forename: Lagnojita
authors.initials: L
authors.lastname: Sinha
authors.affiliation: 1] Biomedical Engineering, Stony Brook University (SUNY), Stony Brook NY 11794 USA [2] Mechanical Engineering, University of Washington, Seattle WA 98195, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Biomedical Engineering, Illinois Institute of Technology, Chicago, IL 60616, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Yang
authors.affiliation: 1] Biomedical Engineering, Stony Brook University (SUNY), Stony Brook NY 11794 USA [2] Mechanical Engineering, University of Washington, Seattle WA 98195, USA.
authors.forename: Altaz
authors.initials: A
authors.lastname: Khan
authors.affiliation: Electrical Engineering, Illinois Institute of Technology, Chicago, IL 60616, USA.
authors.forename: Jovan G
authors.initials: JG
authors.lastname: Brankov
authors.affiliation: 1] Biomedical Engineering, Stony Brook University (SUNY), Stony Brook NY 11794 USA [2] Mechanical Engineering, University of Washington, Seattle WA 98195, USA.
authors.forename: Jonathan T C
authors.initials: JT
authors.lastname: Liu
authors.affiliation: Biomedical Engineering, Illinois Institute of Technology, Chicago, IL 60616, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Tichauer
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery; D003952:Diagnostic Imaging / Q000379:methods*; D066246:ErbB Receptors / Q000378:metabolism*; D005910:Glioma / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery; D008297:Male; D008819:Mice, Nude; D015335:Molecular Probes; D053758:Nanoparticles; D009368:Neoplasm Transplantation; D011485:Protein Binding; D013059:Spectrum Analysis, Raman; D013194:Staining and Labeling; D013514:Surgical Procedures, Operative
chemical_list: D015335:Molecular Probes; C512478:EGFR protein, human; D066246:ErbB Receptors