DNA-Based Photoacoustic Nanosensor for Interferon Gamma Detection

Tracking protein levels in the body is vital in both research and medicine, where understanding their physiological roles provides insight into their regulation in homeostasis and diseases. In medicine, protein levels are actively sampled since they continuously fluctuate, reflecting the status of biological systems and provide insight into patient health. One such protein is interferon gamma, a clinically relevant protein with immunoregulatory functions that play critical roles against infection. New tools for continuously monitoring protein levels in vivo are invaluable in monitoring real-time conditions of patients to allow better care. Here, we developed a DNA-based nanosensor for the photoacoustic detection of interferon gamma. This work demonstrates how we transformed a simple DNA motif, receptors, and a novel phthalocyanine dye into a proof-of-concept photoacoustic nanosensor for protein detection. Surface plasmon resonance kinetic analysis demonstrated that the nanosensor is responsive and reversible to interferon gamma with an affinity in the nanomolar range, K_D1 = 167 nM and K_D2 = 316 nM. As a reporter, our design includes a novel phthalocyanine-based photoacoustic dye that stacks in a J-aggregate, causing a 22.5% increase in signal. Upon receptor binding, the DNA structure bends to induce phthalocyanine dye stacking, resulting in a 55% increase in photoacoustic signal in the presence of 10 μM interferon gamma. This proof-of-concept nanosensor is a novel approach to the development of a photoacoustic sensor and may be adapted for other proteins of interest in the future for in vivo tracking.