Recently, Professor Yi Tao's research group from the College of Chemistry and Chemical Engineering at DHU has made new progress in the field of precision portable diagnosis of early kidney injury. The related research findings, titled "Unimolecular dual-reporter probes for early kidney injury diagnosis through synchronous in situ imaging and portable urinalysis," were published in National Science Review (NSR). This study innovatively proposed a dual-pronged diagnostic strategy of "in vivo in situ tracing + in vitro portable urinalysis," successfully developing a unimolecular dual-reporter probe that is expected to enable precise point-of-care rapid testing before irreversible damage to renal function occurs.
Acute kidney injury (AKI) is a common and critical clinical syndrome, affecting approximately 15% of hospitalized patients and more than 50% of intensive care unit (ICU) patients, with a high mortality rate. However, conventional clinical diagnostic methods rely on indicators such as blood urea nitrogen (BUN) and serum creatinine (SCr), which often do not change significantly until more than half of renal function has been lost. By that time, the kidney has already suffered irreversible damage, making it extremely easy to miss the optimal window for intervention. Therefore, developing methods capable of early and precise diagnosis of kidney injury is of great significance for timely clinical intervention and treatment, as well as for reducing patient mortality risk.
Most conventional kidney injury diagnostic probes adopt a single-reporting mode, being used either for in vivo imaging only or solely for in vitro urinalysis, and thus face problems such as poor diagnostic accuracy and limited specificity. In previous studies, Professor Yi Tao's research group used methylene blue (MB) as a structural core and designed a series of reactive oxygen species (ROS)-responsive controlled-release platforms based on a 2-amino-1,3-benzenedimethanol self-immolative structure, constructing a variety of molecular tools for the diagnosis and treatment of related diseases (Angew. Chem. Int. Ed., 2022, 61, e20211680.; Chem. Sci., 2022, 13, 10815.; J. Control. Release, 2024, 376, 961.; Adv. Mater. 2024, 36, 2309789.; J. Am. Chem. Soc., 2025, 147, 25325-25336.; Angew. Chem. Int. Ed., 2025, 64, e202510441.). On this basis, through modular molecular structure design, this work innovatively integrates three functional units: a photoacoustic signal tracing module (croconic acid, CA), an ROS-activated near-infrared fluorescence module (methylene blue, MB), and a hydrophilicity-regulating kidney-targeting module (PEG), thereby constructing a unimolecular dual-reporter probe, DHU-AKI-3, with activatable, crosstalk-free multiplexed signal output. This probe can be specifically activated by ROS highly expressed in the kidney injury region, simultaneously generating two mutually non-interfering detection signals: the released CA, due to its hydrophobicity, precipitates in situ in the injured kidney, forming a photoacoustic signal that lasts up to 60 hours for long-term in situ monitoring of kidney injury; while the released hydrophilic MB is rapidly excreted in urine, enabling in vitro diagnosis through fluorescence or color changes. This "dual-pronged" design strategy of the unimolecular probe synchronously achieves mutual verification between in vivo in situ photoacoustic signals and in vitro urinalysis signals, thereby improving the accuracy of diagnostic results.
In multiple mouse models (drug-induced kidney injury and unilateral renal ischemia-reperfusion injury), the probe precisely detected the onset of early kidney injury before conventional clinical diagnostic indicators showed significant changes. The research team further developed a smartphone-assisted colorimetric urinalysis method: urine samples need only be dropped onto test strips, images captured with a smartphone camera, and diagnostic results rapidly interpreted using color recognition software. This work not only provides a new molecular tool for early, precise, and portable diagnosis of acute kidney injury, but also offers technical reference for the development of diagnostic technologies in clinical scenarios such as intensive care and post-kidney transplantation monitoring.
Liu Lingyan, Distinguished Associate Research Fellow at the College of Chemistry and Chemical Engineering, Donghua University, and Liu Feiyang, Assistant Professor at the Medical College of Guangxi University, are the co-first authors of the paper. Ding Qihang from Korea University, Associate Professor Wei Peng from Donghua University, Academician Jong Seung Kim from Korea University, and Professor Yi Tao from Donghua University are the co-corresponding authors. Donghua University is the first corresponding institution. This research was supported by the National Key R&D Program and the National Natural Science Foundation of China.
Original link to this article: https://doi.org/10.1093/nsr/nwag367
