TY - JOUR
T1 - Diagnosis of immunomarkers
T2 - In vivo via multiplexed surface enhanced Raman spectroscopy with gold nanostars
AU - Ou, Yu Chuan
AU - Webb, Joseph A.
AU - O'Brien, Christine M.
AU - Pence, Isaac J.
AU - Lin, Eugene C.
AU - Paul, Eden P.
AU - Cole, Danielle
AU - Ou, Shih Hao
AU - Lapierre-Landry, Maryse
AU - Delapp, Rossane C.
AU - Lippmann, Ethan S.
AU - Mahadevan-Jansen, Anita
AU - Bardhan, Rizia
N1 - Funding Information:
YO acknowledges support from American Cancer Society Institutional Research Grant (IRG-58-009-56), National Center for Advancing Translational Sciences CTSA award UL1TR000445, and CDMRP Peer reviewed Cancer research program grant W81XWH-18-1-0139. JAW acknowledges support from the National Science Foundation Graduate Research Fellowship Program under Grant Number 1445197. EP acknowledges support from National Science Foundation grant CMMI-1634856. CMO acknowledges NSF Graduate Research Fellowship. IJP acknowledges support from the National Institute of Health NRSA F31 Fellowship. RCD acknowledges supports from Vanderbilt’s Trans Institutional Programs grant: Materials Durability and Environmental Research Facilities Hub (Faculty PIs - Florence Sanchez and David Kosson). TEM micrographs of AuNS were acquired with an instrument supported by NSF EPS 1004083. TEM images of tumor and organs were acquired by using VUMC Cell Imaging Shared Resource (supported by NIH grants CA68485, DK20593, DK58404, DK59637 and EY08126).
Publisher Copyright:
© 2018 The Royal Society of Chemistry.
PY - 2018/7/21
Y1 - 2018/7/21
N2 - In this work, we demonstrate the targeted diagnosis of immunomarker programmed death ligand 1 (PD-L1) and simultaneous detection of epidermal growth factor receptor (EGFR) in breast cancer tumors in vivo using gold nanostars (AuNS) with multiplexed surface enhanced Raman spectroscopy (SERS). Real-time longitudinal tracking with SERS demonstrated maximum accumulation of AuNS occurred 6 h post intravenous (IV) delivery, enabling detection of both biomarkers simultaneously. Raman signal correlating to both PD-L1 and EGFR decreased by ∼30% in control tumors where receptors were pre-blocked prior to AuNS delivery, indicating both the sensitivity and specificity of SERS in distinguishing tumors with different levels of PD-L1 and EGFR expression. Our in vivo study was combined with the first demonstration of ex vivo SERS spatial maps of whole tumor lesions that provided both a qualitative and quantitative assessment of biomarker status with near cellular-level resolution. High resolution SERS maps also provided an overview of AuNS distribution in tumors which correlated well with the vascular density. Mass spectrometry showed AuNS accumulation in tumor and liver, and clearance via spleen, and electron microscopy revealed AuNS were endocytosed in tumors, Kupffer cells in the liver, and macrophages in the spleen. This study demonstrates that SERS-based diagnosis mediated by AuNS provides an accurate measure of multiple biomarkers both in vivo and ex vivo, which will ultimately enable a clinically-translatable platform for patient-tailored immunotherapies and combination treatments.
AB - In this work, we demonstrate the targeted diagnosis of immunomarker programmed death ligand 1 (PD-L1) and simultaneous detection of epidermal growth factor receptor (EGFR) in breast cancer tumors in vivo using gold nanostars (AuNS) with multiplexed surface enhanced Raman spectroscopy (SERS). Real-time longitudinal tracking with SERS demonstrated maximum accumulation of AuNS occurred 6 h post intravenous (IV) delivery, enabling detection of both biomarkers simultaneously. Raman signal correlating to both PD-L1 and EGFR decreased by ∼30% in control tumors where receptors were pre-blocked prior to AuNS delivery, indicating both the sensitivity and specificity of SERS in distinguishing tumors with different levels of PD-L1 and EGFR expression. Our in vivo study was combined with the first demonstration of ex vivo SERS spatial maps of whole tumor lesions that provided both a qualitative and quantitative assessment of biomarker status with near cellular-level resolution. High resolution SERS maps also provided an overview of AuNS distribution in tumors which correlated well with the vascular density. Mass spectrometry showed AuNS accumulation in tumor and liver, and clearance via spleen, and electron microscopy revealed AuNS were endocytosed in tumors, Kupffer cells in the liver, and macrophages in the spleen. This study demonstrates that SERS-based diagnosis mediated by AuNS provides an accurate measure of multiple biomarkers both in vivo and ex vivo, which will ultimately enable a clinically-translatable platform for patient-tailored immunotherapies and combination treatments.
UR - http://www.scopus.com/inward/record.url?scp=85050027637&partnerID=8YFLogxK
U2 - 10.1039/c8nr01478g
DO - 10.1039/c8nr01478g
M3 - Article
C2 - 29961778
AN - SCOPUS:85050027637
SN - 2040-3364
VL - 10
SP - 13092
EP - 13105
JO - Nanoscale
JF - Nanoscale
IS - 27
ER -