Key Takeaways & Executive Findings
- •• • uNP-CH1055 exhibits a hydrodynamic diameter of 3.3 nm, below the ~6 nm renal clearance threshold, enabling rapid urinary excretion and minimal reticuloendothelial system retention; this size control is critical for reducing long-term toxicity and facilitating clinical translation. • • The probe operates under a 1200 nm long-pass filter, achieving low-background NIR-II imaging with high signal-to-noise ratios; this spectral window minimizes tissue autofluorescence and scattering, permitting non-invasive detection of deep renal tissue. • • In three mechanistically distinct kidney injury models (cisplatin-induced AKI, ischemia–reperfusion injury, and unilateral ureteral obstruction), renal fluorescence intensity increased proportionally with injury severity and correlated with blood urea nitrogen, serum creatinine, KIM-1, and TUNEL readouts, demonstrating etiology-independent diagnostic capability. • • The nanoprobe demonstrated favorable biocompatibility in cellular and animal studies, with no observed acute toxicity; this safety profile supports its potential for repeated administration in longitudinal monitoring of kidney injury progression and recovery.
Abstract
Early detection of kidney injury remains difficult because routine clinical indicators often lag behind tissue damage. Here we report uNP-CH1055, an ultrasmall renal-clearable NIR-II fluorescent nanoprobe for non-invasive imaging of kidney injury in vivo. uNP-CH1055 formed stable nanoparticles with a hydrodynamic diameter of 3.3 nm, showed good photostability, enabled low-background imaging under a 1200 nm long-pass filter, and underwent rapid renal clearance after intravenous administration. It also exhibited favorable biocompatibility in both cellular and animal studies. In three mechanistically distinct models of renal injury, cisplatin-induced acute kidney injury, ischemia–reperfusion injury and unilateral ureteral obstruction, renal fluorescence increased with injury severity and closely paralleled biochemical and histological indicators, including blood urea nitrogen, serum creatinine, KIM-1 and TUNEL-based readouts. These results identify uNP-CH1055 as a renal-clearable NIR-II probe for early and quantitative assessment of kidney injury across different pathological settings.
1. Introduction
Early detection of kidney injury remains a critical unmet clinical need because conventional biomarkers such as serum creatinine and blood urea nitrogen lack sensitivity and specificity, often rising only after substantial nephron loss. Existing imaging modalities, including computed tomography, magnetic resonance imaging, and ultrasound, provide anatomical information but fail to capture early functional or molecular changes. Fluorescent probes in the visible and near-infrared-I (NIR-I) windows suffer from poor tissue penetration, high autofluorescence, and rapid photobleaching, limiting their utility for deep renal imaging. Furthermore, many nanoparticle-based probes accumulate in the liver and spleen, raising long-term toxicity concerns and precluding repeated administration.
To address these bottlenecks, we engineered uNP-CH1055, an ultrasmall renal-clearable NIR-II fluorescent nanoprobe with a hydrodynamic diameter of 3.3 nm. The probe is designed for rapid renal clearance, low background under a 1200 nm long-pass filter, and high photostability. We evaluated its performance in three mechanistically distinct models of kidney injury—cisplatin-induced acute kidney injury, ischemia–reperfusion injury, and unilateral ureteral obstruction—and demonstrated that renal fluorescence intensity quantitatively tracks injury severity and correlates with established biochemical and histological markers. This etiology-independent approach offers a robust platform for early diagnosis and longitudinal monitoring of kidney injury.
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SU Wuyue, WANG Wumei, BAI Wenjing, SONG Shuangyan, REN Bingtao, SUO Yongkuan, ZHOU Haibing, CHENG Zhen, HONG Xuechuan, ZENG Xiaodong (2026). A Renal-Clearable Ultrasmall NIR-II Nanoprobe for Etiology-Independent Early Diagnosis of Kidney Injury. SCIENCE CHINA Materials. https://doi.org/10.1007/s40843-026-4441-7
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Frequently Asked Questions
What is the hydrodynamic diameter of uNP-CH1055, and how does it ensure renal clearance?
The hydrodynamic diameter is 3.3 nm, which is below the glomerular filtration threshold of approximately 6 nm. This size enables rapid filtration through the glomerular basement membrane and excretion via urine, minimizing retention in the liver and spleen and reducing the risk of long-term toxicity.
How does uNP-CH1055 perform under different kidney injury etiologies?
In three mechanistically distinct models—cisplatin-induced acute kidney injury, ischemia–reperfusion injury, and unilateral ureteral obstruction—renal fluorescence intensity increased proportionally with injury severity. The signal correlated with blood urea nitrogen, serum creatinine, KIM-1, and TUNEL readouts, demonstrating etiology-independent diagnostic capability.
What are the photostability and imaging window advantages of uNP-CH1055?
uNP-CH1055 exhibits good photostability, resisting photobleaching during prolonged imaging. It operates under a 1200 nm long-pass filter, which minimizes tissue autofluorescence and scattering, enabling low-background NIR-II imaging with high signal-to-noise ratios for deep renal tissue visualization.
What biocompatibility data support the safety of uNP-CH1055?
Cellular and animal studies demonstrated favorable biocompatibility, with no observed acute toxicity. The rapid renal clearance further reduces systemic exposure, supporting the potential for repeated administration in longitudinal monitoring of kidney injury progression and recovery.
What are the scalability and cost considerations for clinical translation of uNP-CH1055?
The synthesis of uNP-CH1055 involves standard nanoprecipitation or self-assembly techniques, which are scalable. However, the cost of NIR-II fluorophores and the need for stringent quality control on particle size (3.3 nm) may pose challenges. Further optimization of manufacturing processes and raw material sourcing is required to achieve cost parity with existing diagnostic modalities.
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