title: Quantitative molecular phenotyping with topically applied SERS nanoparticles for intraoperative guidance of breast cancer lumpectomy.
abstract: There is a need to image excised tissues during tumor-resection procedures in order to identify residual tumors at the margins and to guide their complete removal. The imaging of dysregulated cell-surface receptors is a potential means of identifying the presence of diseases with high sensitivity and specificity. However, due to heterogeneities in the expression of protein biomarkers in tumors, molecular-imaging technologies should ideally be capable of visualizing a multiplexed panel of cancer biomarkers. Here, we demonstrate that the topical application and quantification of a multiplexed cocktail of receptor-targeted surface-enhanced Raman scattering (SERS) nanoparticles (NPs) enables rapid quantitative molecular phenotyping (QMP) of the surface of freshly excised tissues to determine the presence of disease. In order to mitigate the ambiguity due to nonspecific sources of contrast such as off-target binding or uneven delivery, a ratiometric method is employed to quantify the specific vs. nonspecific binding of the multiplexed NPs. Validation experiments with human tumor cell lines, fresh human tumor xenografts in mice, and fresh human breast specimens demonstrate that QMP imaging of excised tissues agrees with flow cytometry and immunohistochemistry, and that this technique may be achieved in less than 15 minutes for potential intraoperative use in guiding breast-conserving surgeries.
authors.affiliation: Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Biomedical Engineering, Stony Brook University (SUNY), Stony Brook, NY 11794, USA.
authors.forename: Altaz
authors.initials: A
authors.lastname: Khan
authors.affiliation: Department of Biomedical Engineering, Stony Brook University (SUNY), Stony Brook, NY 11794, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Ruttner
authors.affiliation: Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA.|Department of Biomedical Engineering, Stony Brook University (SUNY), Stony Brook, NY 11794, USA.
authors.forename: Steven Y
authors.initials: SY
authors.lastname: Leigh
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Murray
authors.affiliation: Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Sanjee
authors.initials: S
authors.lastname: Abeytunge
authors.affiliation: Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Peterson
authors.affiliation: Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Milind
authors.initials: M
authors.lastname: Rajadhyaksha
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Dintzis
authors.affiliation: Department of Surgery, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Javid
authors.affiliation: Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Jonathan T C
authors.initials: JT
authors.lastname: Liu
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000601:surgery*; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D000072662:Margins of Excision; D015412:Mastectomy, Segmental / Q000379:methods*; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000378:metabolism; D013059:Spectrum Analysis, Raman / Q000379:methods*; D025321:Surgery, Computer-Assisted
chemical_list: D014408:Biomarkers, Tumor; D011956:Receptors, Cell Surface