Abstract 1934: Development of spectrally distinct silica coated gold nanorods for detection of cancer using MSOT

Abstract

Abstract Traditional cancer imaging devices are limited in their ability to screen for multiple contrast agents simultaneously in real time. Multispectral Optoacoustic Tomography (MSOT) is an emerging imaging modality capable of real-time imaging of numerous contrast agents with enhanced spatial resolution of 75µm at depths of 5 cm. The use of exogenous contrast agents in MSOT remains largely unexplored, so we developed two species of spectrally distinct gold nanorod as contrast agents for use in MSOT. Our goal was to evaluate the potential of MSOT to spectrally differentiate two exogenous contrast agents simultaneously. Two gold nanorod species were created using hydrogen peroxide (GNR-H2O2) or ascorbic (GNR-ASC) acid as reducing agents to modify the length of each species to create nanorods with individual light absorbance spectra in the IR range (680-900 nm). These gold nanorods were highly stabilized via encapsulation with mesoporous silica along with a subsequent chitosan capping. Human epidermal growth factor receptor 2 positive (HER2+) cells were specifically targeted by conjugating these mesoporous silica-coated chitosan capped gold nanorods (CMGs) to Trastuzumab resulting in TRA-CMG particles. Both TRA-CMG-ASC and TRA-CMG-H2O2 resulted in optoacoustic spectrally distinct signals when imaged in tissue phantoms both individually as well as mixed within the same well after multispectral processing using linear regression. Treatment of HER2+ breast cancer cell lines, DY36T2Q and SKBR3, with TRA-CMG-H2O2 resulted in 2.5x and 3.1x enhanced signal, respectively, as compared to HER2- MDA-MD468 cells. Treatment of DY36T2Q and SKBR3 cells with TRA-CMG-ASC demonstrated 3.7x and 6.9x, respectively, compared to MDA-MD468. In all three cell lines treated with a combination of TRA-CMG-H2O2’s and TRA-CMG-ASC’s clear and distinct signals were observed for each particle, demonstrating that each TRA-CMG possessed and maintained a detectibly distinct optoacoustic spectrum, in the IR range, allowing them to be detectable as separate contrast agents in MSOT while proximate to other targeted contrast agents. Both particles have demonstrated that they can be simultaneously administered and targeted at HER2+ cell while also maintaining distinct photoacoustic signals in MSOT upon consolidation. Each particle species, targeted to the same cells, were capable of being monitored individually in the presence of the other gold nanorod contrast agent. Citation Format: Karl N. Thomas, Abhilash Samykutty, Molly McNally, Lacey R. McNally. Development of spectrally distinct silica coated gold nanorods for detection of cancer using MSOT [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1934.