(676f) Pinpointed Diagnosis of Early Stage Oral Cancer by Optical Coherence Tomography Using Stimuli-Disassembling Gold Nanoclusters

Early, accurate, and non-invasive (or minimally invasive) diagnosis plays a determining role in achieving an effective treatment and prognosis of cancer. Optical coherence tomography (OCT) offers almost non-invasive and real time monitoring of cancer pathology with micrometer resolution. A pivotal challenge in OCT imaging is to obtain the maximum signals to noise ratio due to optical interference with heterogeneous tissue structures and fluid movements. Gold nanoparticles (Au NPs) have been increasingly employed as optical contrast agents for their superior optical properties and high biocompatibility. However, they are generally not responsive to pathological triggers. In this study, Au NPs were clustered to form gold nanoclusters (Au NCs) via linkers that are cleavable in tumor. Upon disassembly in cancerous microenvironment such as mildly acidic pH, Au NCs are designed to generate two distinctive and quantitative signal changes: Lowered scattering and increased Doppler variance. Au NCs were synthesized by conjugating activated Au NPs via acid-cleavable ketal linkages. Dynamic light scattering (DLS) particle analysis, transmission electron microscopy (TEM), and UV/Vis spectroscopy confirmed acid-triggered disassembly of Au NCs in addition to successful synthesis. The stimuli-triggered Au NC disassembly was simulated efficient in a phantom tissue under an acidic condition. The novel concept developed in this study was finally demonstrated using a hamster oral cancer model. Significantly diminished OCT signals along with distinctively increased Doppler variance OCT signals after administering stimuli-disassembling Au NCs clearly pinpointed early stage cancer, while no such changes were observed after administering non-disassembling Au NCs. This talk will exemplify the crucial and indispensable roles of combining interdisciplinary principles of engineering, physics, and medicine in developing technologies for an accurate detection of early stage cancer.