Responsive Probes for In Vivo Magnetic Resonance Imaging of Nitric Oxide

Nitric oxide (NO), a pivotal signaling molecule, plays multifaceted roles in physiological and pathological processes, including cardiovascular and immune functions, neurotransmission, and cancer progression. Nevertheless, measuring NO in vivo is challenging due to its transient nature and the complexity of the biological environment. Here we describe NO-responsive magnetic probes made of crosslinked superparamagnetic iron oxide nanoparticles tethered to a NO-sensitive cleavable linker for highly sensitive and selective NO magnetic resonance imaging in vivo. These probes enable the detection of NO at concentrations as low as 0.147 μM, allowing for the imaging and quantification of NO in mouse tumor models, studying its effects on tumor progression and immunity, and assessing the response of tumor-associated macrophages to cancer immunotherapeutic agents. Additionally, they facilitate concurrent anatomical and molecular imaging of organs, helping to identify pathological alterations in the liver. Overall, these probes represent promising non-invasive tools for investigating the dose-dependent conflicting role of NO in physiological and pathophysiological processes.