Development of Near-Infrared Photothermal Chemiluminescent Gold Nanoprobes by Utilizing Retro Diels-Alder Reaction of Trapped Singlet Oxygens

PROJECT SUMMARY Bioluminescence imaging (BLI) is widely used for cancer detection and treatment monitoring, but its effectiveness is significantly reduced in hypoxic tumor environments due to the oxygen dependency of traditional luciferase-luciferin reactions. This leads to weak signals and inaccurate imaging, making it difficult to detect and monitor tumors in oxygen-deficient areas. This project aims to overcome these limitations by developing oxygen-independent chitosan-coated gold nanorods (Au-CNRs) that enhance chemiluminescence (CL) imaging precision in hypoxic conditions. These Au- CNRs are designed to trigger a photothermal effect upon near-infrared (NIR) light exposure, releasing singlet oxygen (¹O₂) and producing CL without relying on oxygen. This innovative approach will enable deeper tissue penetration, higher signal-to-noise ratios (SNR), and improved imaging accuracy in both normoxic and hypoxic environments. Key innovations of this project include eliminating the dependency on oxygen and reactive oxygen species (ROS), enabling precise, on-demand ¹O₂ release through NIR irradiation. This results in strong NIR CL at the tumor site, reducing background noise and increasing image specificity and contrast. The Au-CNRs are also biocompatible, stable at room temperature, and minimize toxicity risks compared to conventional inorganic imaging agents. The project will involve synthesizing pyridone-based ¹O₂ release agents with enhanced thermal stability, which will be conjugated to Au-CNRs. These Au-CNRs will be characterized using techniques such as UV-Vis spectroscopy, FTIR, TEM, DLS, and zeta potential measurements. Photothermal studies will evaluate CL intensities, on/off control cycles, and temperature regulation under NIR light to ensure efficient, tumor-specific activation and high-contrast imaging. The expected outcomes include the successful development of thermally stable ¹O₂ release agents and Au- CNRs capable of controlled, NIR-triggered CL in hypoxic tumor environments. This technology has the potential to revolutionize luminescence imaging by enhancing cancer detection and monitoring, particularly in challenging hypoxic conditions, ultimately leading to improved treatment planning and outcomes for patients.