Oral Nanoaggregate Probe for Noninvasive Urinalysis of Acute Kidney Injury

As a noninvasive diagnostic method, oral-to-urinalysis demonstrates significant application potential due to its combination of operational convenience and safety. Herein, we report a nanoaggregate probe (MB-ES) for the early noninvasive diagnosis of acute kidney injury (AKI) via the oral-to-urinalysis approach. MB-ES exhibits favorable oral applicability and can be specifically activated by esterase to release methylene blue (MB). Owing to the high hydrophobicity of MB-ES (Clog P = 4.94), it self-assembles into nanoaggregates (hydrodynamic diameter ≈ 644.9 nm) in aqueous environments, thereby limiting nonspecific uptake by intestinal epithelial cells after oral administration in mice. Under the action of intestinal esterase, MB-ES is specifically hydrolyzed to release MB, which is then taken up and cleared into the urine via the kidneys. In AKI model mice, the decrease in glomerular filtration rate leads to a significant reduction in urinary MB, enabling urinalysis-based diagnosis. More importantly, this method detects abnormalities within 6 h after the onset of AKI, 42 h earlier than traditional methods, providing a critical window for early intervention. Furthermore, we translated this strategy into a test strip-based colorimetric assay and established a portable platform for renal function assessment. Together, MB-ES-based oral-to-urinalysis method combines noninvasiveness, ultraearly warning, and convenience, offering a practical tool for the early screening of AKI.