Abstract
A key design consideration in developing contrast agents is obtaining distinct, multiple signal changes in diseased tissue. Plasmonic gold nanoparticles (Au NPs) have been developed as contrast agents due to their strong surface plasmon resonance (SPR). This study aims to demonstrate that stimuli-responsive plasmonic Au nanoclusters (Au NCs) can be used as a contrast agent for optical coherence tomography (OCT) in detecting early-stage cancer. Au NPs were clustered via acid-cleavable linkers to synthesize Au NCs that disassemble under mildly acidic conditions into individual Au NPs, simultaneously diminishing SPR effect (quantified by scattering intensity) and increasing Brownian motion (quantified by Doppler variance). The acid-triggered morphological and accompanying optico-physical property changes of the acid-disassembling Au NCs were confirmed by TEM, DLS, UV/Vis, and OCT. Stimuli-responsive Au NCs were applied in a hamster check pouch model carrying early-stage squamous carcinoma tissue. The tissue was visualized by OCT imaging, which showed reduced scattering intensity and increased Doppler variance in the dysplastic tissue. This study demonstrates the promise of diagnosing early-stage cancer using molecularly programmable, inorganic nanomaterial-based contrast agents that are capable of generating multiple, stimuli-triggered diagnostic signals in early-stage cancer.
Highlights
Unique and tunable optical properties [e.g., surface plasmon resonance (SPR) effect] without obstruction by photo-bleaching or photo-blinking have made plasmonic inorganic nanoparticles (NPs) an attractive, popularlyinvestigated nanomaterial for biomedical imaging applications including optical imaging [1]
In order to meet the design goals of this study, Au nanoclusters (Au NCs) needed to be composed of small Au NPs of the minimally required size for detection by optical coherence tomography (OCT) and Doppler variance OCT images (DvOCT)
polyethylene glycol (PEG) was conjugated on the surface of Au NCs to prevent aggregation, under biological/physiological conditions [44]
Summary
Unique and tunable optical properties [e.g., surface plasmon resonance (SPR) effect] without obstruction by photo-bleaching or photo-blinking have made plasmonic inorganic nanoparticles (NPs) an attractive, popularlyinvestigated nanomaterial for biomedical imaging applications including optical imaging [1]. Kim et al Nano Convergence (2018) 5:3 limitation affects OCT diagnostic performance for early-stage cancer; it can potentially be overcome by using optical contrast agents such as Au NPs [3, 23,24,25,26]. Plasmonic Au nanoclusters (NCs) that transform their physical and optical properties upon detecting a stimulus (e.g., mildly acidic pH of tumor tissue [28,29,30]) in a diseased area are highly promising OCT contrast agents due to their ability to improve OCT imaging with enhanced SPR effects [31, 32]. We synthesized Au NCs by using an acid-cleavable linker to cluster individual Au NPs
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