title: Gd2O3-doped silica @ Au nanoparticles for in vitro imaging cancer biomarkers using surface-enhanced Raman scattering.
abstract: There has been an interest in developing multimodal approaches to combine the advantages of individual imaging modalities, as well as to compensate for respective weaknesses. We previously reported a composite nano-system composed of gadolinium-doped mesoporous silica nanoparticle and gold nanoparticle (Gd-Au NPs) as an efficient MRI contrast agent for in vivo cancer imaging. However, MRI lacks sensitivity and is unsuitable for in vitro cancer detection. Thus, here we performed a study to use the Gd-Au NPs for detection and imaging of a widely recognized human cancer biomarker, epidermal growth factor receptor (EGFR), in individual human cancer cells with surface-enhanced Raman scattering (SERS). The Gd-Au NPs were sequentially conjugated with a monoclonal antibody recognizing EGFR and a Raman reporter molecule, 4-meraptobenzoic acid (MBA), to generate a characteristic SERS signal at 1075cm-1. By spatially mapping the SERS intensity at 1075cm-1, cellular distribution of EGFR and its relocalization on the plasma membrane were measured in situ. In addition, the EGFR expression levels in three human cancer cell lines (S18, A431 and A549) were measured using this SERS probe, which were consistent with the comparable measurements using immunoblotting and immunofluorescence. Our SERS results show that functionalized Gd-Au NPs successfully targeted EGFR molecules in three human cancer cell lines and monitored changes in single cell EGFR distribution in situ, demonstrating its potential to study cell activity under physiological conditions. This SERS study, combined with our previous MRI study, suggests the Gd-Au nanocomposite is a promising candidate contrast agent for multimodal cancer imaging.
authors.affiliation: Department of Biological Engineering, Utah State University, Logan, UT 84322-4105, USA.
authors.forename: Lifu
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Biomedical Engineering, Guangzhou Medical College, Guangzhou 510182, People's Republic of China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Cancer Biology, The University of Kansas Medical Center and The University of Kansas Cancer Center, Kansas City, KS 66160, USA.
authors.forename: Sitaram
authors.initials: S
authors.lastname: Harihar
authors.affiliation: Department of Biological Engineering, Utah State University, Logan, UT 84322-4105, USA; Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, No.59, Xiangzhu Road, Nanning 530003, Guangxi, People's Republic of China.
authors.forename: Qifei
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Cancer Biology, The University of Kansas Medical Center and The University of Kansas Cancer Center, Kansas City, KS 66160, USA.
authors.forename: Danny R
authors.initials: DR
authors.lastname: Welch
authors.affiliation: Department of Biological Engineering, Utah State University, Logan, UT 84322-4105, USA. Electronic address: Anhong.Zhou@usu.edu.
authors.forename: Anhong
authors.initials: A
authors.lastname: Zhou
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics; D066246:ErbB Receptors / Q000378:metabolism; D005682:Gadolinium / Q000737:chemistry / Q000493:pharmacokinetics; D006046:Gold / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D053761:Nanocomposites / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry* / Q000493:pharmacokinetics; D013059:Spectrum Analysis, Raman / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D003287:Contrast Media; D006046:Gold; D012822:Silicon Dioxide; D005682:Gadolinium; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Epidermal growth factor receptor; Gadolinium-gold nanoparticles; Human cancer cells; Surface-enhanced Raman scattering