Esophageal squamous cell carcinoma (ESCC) is responsible for approximately one-sixth of all cancer-related deaths worldwide. This malignancy is due to several environmental, dietary and genetic factors. Since esophageal cancer has often metastasized at the time of diagnosis, current treatment modalities offer poor survival and cure rates. There is a need for improved imaging diagnostics to screen for subtle changes that precede the onset of ESCC. Since ESCC originates from the squamous cells that line the inner surface of the esophagus, the imaging of altered protein expression (molecular biomarkers) at these surfaces could be used to monitor disease progression. However, due to the variability in molecular expression patterns between patients, and within a single patient over time, accurate disease diagnosis would benefit from the ability to image a large number of molecular targets. Therefore, we are developing an in vivo imaging device to image surface-enhanced Raman scattering (SERS) nanoparticles that are capable of being highly multiplexed to target a large number of protein biomarkers. This feasibility study will develop and demonstrate these technologies in a well-established rat model of ESCC. This two-year exploratory study will develop technologies, and provide evidence of feasibility, to enable future studies to visualize alterations in molecular expression that occur during the progression of ESCC in a rat model, as well as to investigate the molecular changes that occur in response to therapy. In the future, we will work with collaborators to develop SERS particles to target a variety of biomarkers that are relevant for this cancer model, as well as in humans. Our ultimate goal is to better understand the molecular transformations associated with cancer progression in this rat model as well as in human esophageal cancers, thus enabling accurate early detection, assessment of therapy response, and personalized treatments. Efforts are being made, including toxicity studies, to secure FDA approval for the translation of these imaging devices and nanoparticles into humans.
We propose to develop a portable endoscopic device to image molecularly-targeted surface enhanced Raman scattering (SERS) particles that act as nano-sized barcodes to enable the visualization of a multiplexed panel of protein biomarkers expressed in the esophagus of rats that develop esophageal squamous cell carcinoma. These technologies will enable real-time non-invasive imaging of large numbers of molecular biomarkers for the early detection of diseases, assessment of molecular changes in response to therapy, and for guiding personalized treatment regimens. These technologies are ultimately intended for translation into humans; toxicity studies are being performed and FDA approval is being sought for the nanoparticles.
|Kang, Soyoung; Wang, Yu Winston; Xu, Xiaochun et al. (2018) Microscopic investigation of"" topically applied nanoparticles for molecular imaging of fresh tissue surfaces. J Biophotonics 11:e201700246|
|Wang, Yu Winston; Reder, Nicholas P; Kang, Soyoung et al. (2017) Raman-Encoded Molecular Imaging with Topically Applied SERS Nanoparticles for Intraoperative Guidance of Lumpectomy. Cancer Res 77:4506-4516|
|Xu, Xiaochun; Wang, Yu; Xiang, Jialing et al. (2017) Rinsing paired-agent model (RPAM) to quantify cell-surface receptor concentrations in topical staining applications of thick tissues. Phys Med Biol 62:5098-5113|
|Wang, Yu W; Doerksen, Josh D; Kang, Soyoung et al. (2016) Multiplexed Molecular Imaging of Fresh Tissue Surfaces Enabled by Convection-Enhanced Topical Staining with SERS-Coded Nanoparticles. Small 12:5612-5621|
|Wang, Yu; Kang, Soyoung; Khan, Altaz et al. (2016) Quantitative molecular phenotyping with topically applied SERS nanoparticles for intraoperative guidance of breast cancer lumpectomy. Sci Rep 6:21242|
|Wang, Yu; Kang, Soyoung; Doerksen, Josh D et al. (2016) Surgical Guidance via Multiplexed Molecular Imaging of Fresh Tissues Labeled with SERS-Coded Nanoparticles. IEEE J Sel Top Quantum Electron 22:|
|Kang, Soyoung; Wang, Yu; Reder, Nicholas P et al. (2016) Multiplexed Molecular Imaging of Biomarker-Targeted SERS Nanoparticles on Fresh Tissue Specimens with Channel-Compressed Spectrometry. PLoS One 11:e0163473|
|Wang, Yu Winston; Kang, Soyoung; Khan, Altaz et al. (2015) In vivo multiplexed molecular imaging of esophageal cancer via spectral endoscopy of topically applied SERS nanoparticles. Biomed Opt Express 6:3714-23|
|Garai, Ellis; Sensarn, Steven; Zavaleta, Cristina L et al. (2015) A real-time clinical endoscopic system for intraluminal, multiplexed imaging of surface-enhanced Raman scattering nanoparticles. PLoS One 10:e0123185|
|Sinha, Lagnojita; Wang, Yu; Yang, Cynthia et al. (2015) Quantification of the binding potential of cell-surface receptors in fresh excised specimens via dual-probe modeling of SERS nanoparticles. Sci Rep 5:8582|
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