In vivo multiplexed molecular imaging of esophageal cancer via spectral endoscopy of topically applied SERS nanoparticles

Abstract

The biological investigation and detection of esophageal cancers could be facilitated with an endoscopic technology to screen for the molecular changes that precede and accompany the onset of cancer. Surface-enhanced Raman scattering (SERS) nanoparticles (NPs) have the potential to improve cancer detection and investigation through the sensitive and multiplexed detection of cell-surface biomarkers. Here, we demonstrate that the topical application and endoscopic imaging of a multiplexed cocktail of receptor-targeted SERS NPs enables the rapid detection of tumors in an orthotopic rat model of esophageal cancer. Antibody-conjugated SERS NPs were topically applied on the lumenal surface of the rat esophagus to target EGFR and HER2, and a miniature spectral endoscope featuring rotational scanning and axial pull-back was employed to comprehensively image the NPs bound on the lumen of the esophagus. Ratiometric analyses of specific vs. nonspecific binding enabled the visualization of tumor locations and the quantification of biomarker expression in agreement with immunohistochemistry and flow cytometry validation data.

Rinsing paired-agent model (RPAM) to quantify cell-surface receptor concentrations in topical staining applications of thick tissues

“…However, it should be noted that the receptor concentrations estimated using both pairs of imaging agents for the two cell lines in all conditions, matched well with expected levels of EGFR. These agents have also been used extensively and validated in other work, where EGFR concentrations matched well with gold standard and expected levels (Leigh et al , 2013; Wang et al , 2016; Wang et al , 2015; Wang et al , 2014b; Tichauer et al , 2012a; Tichauer et al , 2012b; Samkoe et al , 2014). This body of work suggests that both non-specific binding and internalization are relatively negligible, at least within 1 h of initial administration of the imaging agents.…”

“…Recent work has established the potential for paired-agent methods to overcome the limitations of direct topical staining of thick tissues (Davis et al , 2013; Liu et al , 2009; Sinha et al , 2015; Wang et al , 2014a; Wang et al , 2016; Wang et al , 2015). Such methods utilize the signal from a control (untargeted) imaging agent that is co-administered with one or more targeted agent(s) to account for background staining and variable optical properties (Tichauer et al , 2015).…”

“…Furthermore, it can only analyze serial rinsing data in which each rinse step is identical, a requirement that can be difficult to achieve in certain applications. All other paired-agent applications have employed very simple, quick, and relatively noise-insensitive, “non-kinetic-modeling” ratiometric approaches (Davis et al , 2013; Liu et al , 2009; Wang et al , 2015; Wang et al , 2016): i.e. , dividing the targeted agent signal by the control agent signal (ratiometric).…”

Surface-enhanced Raman spectroscopy for in vivo biosensing

“…The method is also applicable to esophageal cancer, with multiplexed detection of HER2 and EGFR being possible after topical application of targeted SERS NPs and detection with an endoscopic probe. 130 These studies demonstrated the suitability for in vivo SERS-based cancer detection in relation to gastrointestinal tract cancers, which can be easily surveyed using endoscopic systems with Raman modality. Any tissues accessible to an endoscope could be probed in this manner, including skin, bladder, stomach, lungs, esophagus, cervix and vagina, and with many of the endoscopic Raman probes being approved for clinical use, the major barrier to surmount for this approach now surrounds nanoprobe toxicity.…”

Multimodality Raman and photoacoustic imaging of surface-enhanced-Raman-scattering-targeted tumor cells

“…[1][2][3][4][5][6][7][8][9][10][11][12][13] Fluorescence-based detection suffers from significant background autofluorescence.…”