Real-Time Monitoring Renal Impairment Due to Drug-Induced AKI and Diabetes-Caused CKD Using an NAG-Activatable NIR-II Nanoprobe
Abstract
Real-time in vivo optical imaging of kidney function is important for the diagnosis of renal diseases, such as acute kidney injury (AKI) and chronic kidney disease (CKD), with high morbidity and mortality worldwide. However, the reported optical imaging agents still have limitations for identifying AKI or CKD in the early stage due to their low sensitivity, poor tissue penetration, and significant background interference. Herein, an N -acetyl-β- d -glucosaminidase (NAG)-activatable second near-infrared (NIR-II) fluorescent nanoprobe (BOD-II-NAG-NP) is developed for monitoring the progression of drug-induced AKI and in vivo imaging of diabetes-caused CKD. NAG, as a biomarker of renal diseases, is able to specifically activate BOD-II-NAG-NP to release NIR-II fluorescence signals, enabling in vivo imaging of kidney dysfunctions in living mice. Importantly, such an active imaging mechanism allows BOD-II-NAG-NP to noninvasively detect the onset of drug-induced AKI at least 32 h earlier than the most existing assays, which indicates that BOD-II-NAG-NP has the potential to be an optical imaging agent for the early diagnosis of AKI. Moreover, NIR-II fluorescence produced by BOD-II-NAG-NP could deeply penetrate into the relatively thick layers of fat in diabetic nephropathy mice and provide in vivo imaging with high resolution, indicating that BOD-II-NAG-NP has clinical potential for precision diagnosis of CKD.
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In cisplatin-induced AKI models, BOD-II-NAG-NP enabled high-resolution imaging within 5 min post injection, with signals localized predominantly in the kidneys.
“In cisplatin-induced AKI models, BOD-II-NAG-NP enabled high-resolution imaging within 5 min post injection, with signals localized predominantly in the kidneys.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [209]
In the high-fat diet-induced diabetic nephropathy model, NIR-II fluorescence generated by BOD-II-NAG-NP could penetrate through the thicker fat layer, achieving clear imaging.
“Notably, in the high-fat diet-induced diabetic nephropathy model, the NIR-II fluorescence generated by BOD-II-NAG-NP could penetrate through the thicker fat layer, achieving clear imaging.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [209]
In vivo NIR-II imaging of NAG held clinical application prospects for achieving early and accurate diagnosis of AKI and CKD.
“These results indicated that in vivo NIR-II imaging of NAG held clinical application prospects for achieving early and accurate diagnosis of AKI and CKD.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [209]
Fluorescence titration revealed that addition of NAG led to significant enhancement of BOD-II-NAG fluorescence intensity at 1000 nm, with a detection limit of 0.72 mU/mL.
“Fluorescence titration revealed that the addition of NAG led to a significant enhancement of its fluorescence intensity at 1000 nm, with a detection limit of 0.72 mU/mL.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [209]
BOD-II-NAG was conjugated with mPEG-DSPE to form water-dispersible BOD-II-NAG-NP.
“To improve biocompatibility, BOD-II-NAG was conjugated with mPEG-DSPE to form water-dispersible BOD-II-NAG-NP.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [209]
Gu et al. developed BOD-II-NAG, a novel NIR-II fluorescent probe that could be activated by N-acetyl-β-D-glucosaminidase (NAG).
“Gu et al. developed BOD-II-NAG, a novel NIR-II fluorescent probe that could be activated by N-acetyl-β-D-glucosaminidase (NAG) (Fig. 16a)209.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [209]
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Renal-clearable probes for in vivo imaging of acute kidney injury
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A Versatile Aza-BODIPY-Based Activatable Probe for High-Contrast NIR-II Biosensing
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- Authors
- Tan, J., Yin, K., Ouyang, Z., Wang, R., Pan, H., Wang, Z., Zhao, C., Guo, W., & Gu, X.
- Affiliations
- Fudan University (CN)
- East China University of Science and Technology (CN)
- Corresponding author
- Guo, Wei
- Gu, Xianfeng
- Venue
- Analytical Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2021-11-23
- Volume
- 93
- Issue
- 48
- Pages
- 16158-16165
- ISSN
- 0003-2700 (ISSN-L)
- 1520-6882
- OpenAlex
- W3215218443
- Cited by
- 52
- References
- 44
- Citations by year
- 2026: 17 · 2025: 13 · 2024: 6 · 2023: 8 · 2022: 8
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Analytical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Science and Technology Commission of Shanghai Municipality (2018SHZDZX03)
- National Natural Science Foundation of China (21572039, 21874043, 21977018)
- Topics
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Physical Sciences › Chemistry › Spectroscopy › Molecular Sensors and Ion Detection
- Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
- Keywords
- drug-induced acute kidney injury, chronic kidney disease, diabetic nephropathy, N-acetyl-beta-D-glucosaminidase, early diagnosis of kidney disease, renal function monitoring
- MeSH terms
- Acetylglucosaminidase, Animals, Diabetes Mellitus, Pharmaceutical Preparations, Biomarkers, Mice, Renal Insufficiency, Chronic, Acute Kidney Injury
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