NIR-II Photoacoustic Reporter for Biopsy-Free and Real-Time Assessment of Wilson's Disease

Abstract

Wilson's disease (WD) is a rare inherited disorder of copper metabolism with pathological copper hyperaccumulation in some vital organs. However, the clinical diagnosis technique of WD is complicated, aggressive, and time-consuming. In this work, a novel ratiometric photoacoustic (PA) imaging nanoprobe in the NIR-II window is developed to achieve noninvasive, rapid, and accurate Cu²⁺ quantitative detection in vitro and in vivo. The nanoprobe consists of Cu²⁺ -responsive IR970 dye and a nonresponsive palladium-coated gold nanorod (AuNR-Pd), achieving a concentration-dependent ratiometric PA₉₇₀ /PA₁₂₆₀ signal change. The urinary Cu²⁺ content is detectable within minutes down to a detection limit of 76 × 10^-9 m. This report acquisition time is several orders of magnitude shorter than those of existing detection approaches requiring complex procedure. Moreover, utilizing the ratiometric PA nanoprobe, PA imaging enables biopsy-free measurement of the liver Cu²⁺ content and visualization of the liver Cu²⁺ biodistribution of WD patient, which avoid the body injury during the clinical Cu²⁺ test using liver biopsy method. The NIR-II ratiometric PA detection method is simple and noninvasive with super precision, celerity, and simplification, which holds great promise as an alternative to liver biopsy for clinical diagnosis of WD.

Keywords: NIR-II; Wilson's disease; biosensing; photoacoustic imaging; ratiometric nanoprobe.