Ratiometric Photoacoustic Nanoprobe for Bioimaging of Cu²

Aberrant copper contents implicate numerous diseases including Alzheimer's disease and Wilson's disease. Conventional copper detection technologies are difficult to offer non-invasive and accurate deep tissue detection of copper. Here, we report a photoacoustic (PA) nanoprobe (NRh-IR-NMs) for ratiometric PA imaging of Cu²⁺. The nanoprobe consists of a selective Cu²⁺-responsive probe (NRh) as the indicator and a nonresponsive dye (IR) as the internal reference. In the presence of Cu²⁺, a selective Cu²⁺-induced structure change of NRh would take place, resulting in the increase of PA signal intensity increment at 716 nm (ΔPA716). However, the ΔPA834 which attributes to IR shows negligible change. Therefore, the ratiometric PA signal (ΔPA716/ΔPA834) could be used as an indicator for Cu²⁺ detection. This ratiometric PA detection method offers a noninvasive technology with high selectivity and tissue penetration depth, which is a promising tool for deep-tissue detection of Cu²⁺ in living organisms.