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Peer-reviewedCC BY 4.0Advanced Science

Self‐Amplified Activatable Fluorescent Probe for Early Diagnosis of Acute Kidney Injury and High‐Throughput Screening of Natural Protectants

  1. 1Key Laboratory of Biomaterials of Guangdong Higher Education Institutes Department of Biomedical Engineering and MOE Key Laboratory of Tumor Molecular Biology Jinan University Guangzhou People's Republic of China
  2. 2Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction The Fifth Affiliated Hospital of Jinan University (Heyuan Shenhe People's Hospital) Jinan University Heyuan People's Republic of China
  3. 3School of Biomedical Sciences and Engineering Guangzhou International Campus South China University of Technology Guangzhou People's Republic of China

Abstract

Early diagnosis of acute kidney injury (AKI) and identification of effective therapeutics remain significant clinical challenges. Herein, we developed an activatable near‐infrared fluorescent nanoprobe (denoted PS‐QRC) by encapsulating a self‐amplifying fluorescent sensor (QRCy) within kidney‐targetable L‐serine‐functionalized ultrasmall poly(amidoamine) (PAMAM‐Ser) dendrimers. Upon activation by reactive oxygen species (ROS), QRCy undergoes self‐fragmentation, releasing four fluorophores to amplify the fluorescence signal, affording an ultra‐low detection limit of 81 nM for hydrogen peroxide. The L‐serine modification enables specific binding of PS‐QRC to kidney injury molecule‐1 (KIM‐1), which is overexpressed in injured renal tubules, thereby promoting renal accumulation and reducing background interference. Impressively, PS‐QRC allows noninvasive real‐time imaging of cisplatin‐induced AKI in mice as early as 12 h, significantly earlier than conventional serum biochemical and histopathological analyses. Furthermore, a high‐throughput screening platform was established using this nanoprobe to evaluate natural products, from which chrysin was identified as a promising renoprotective agent. Chrysin demonstrated both in vitro and in vivo renoprotective effects, with efficacy comparable to the established antioxidant N‐acetylcysteine. Moreover, PS‐QRC enabled quantitative monitoring of chrysin's dose‐dependent therapeutic response. Overall, this integrated probe provides a sensitive and reliable tool for early AKI diagnosis and the high‐throughput discovery of novel renoprotective drugs.

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BibTeX
@article{chen2026selfamplified,
  title = {{Self‐Amplified Activatable Fluorescent Probe for Early Diagnosis of Acute Kidney Injury and High‐Throughput Screening of Natural Protectants}},
  author = {Yahui Chen and Meihong Liu and Mengchao Ding and Ye Liu and Chuanxu Zhu and Mingye Gong and Zhixuan Huang and Yi Zhang and Wei Xue and Youyong Yuan and Kewei Wang},
  journal = {Advanced Science},
  year = {2026},
  month = aug,
  doi = {10.1002/advs.77162},
  url = {https://doi.org/10.1002/advs.77162},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Self‐Amplified Activatable Fluorescent Probe for Early Diagnosis of Acute Kidney Injury and High‐Throughput Screening of Natural Protectants
AU  - Yahui Chen
AU  - Meihong Liu
AU  - Mengchao Ding
AU  - Ye Liu
AU  - Chuanxu Zhu
AU  - Mingye Gong
AU  - Zhixuan Huang
AU  - Yi Zhang
AU  - Wei Xue
AU  - Youyong Yuan
AU  - Kewei Wang
PY  - 2026
DA  - 2026/08/13
JO  - Advanced Science
DO  - 10.1002/advs.77162
UR  - https://doi.org/10.1002/advs.77162
AB  - Early diagnosis of acute kidney injury (AKI) and identification of effective therapeutics remain significant clinical challenges. Herein, we developed an activatable near‐infrared fluorescent nanoprobe (denoted PS‐QRC) by encapsulating a self‐amplifying fluorescent sensor (QRCy) within kidney‐targetable L‐serine‐functionalized ultrasmall poly(amidoamine) (PAMAM‐Ser) dendrimers. Upon activation by reactive oxygen species (ROS), QRCy undergoes self‐fragmentation, releasing four fluorophores to amplify the fluorescence signal, affording an ultra‐low detection limit of 81 nM for hydrogen peroxide. The L‐serine modification enables specific binding of PS‐QRC to kidney injury molecule‐1 (KIM‐1), which is overexpressed in injured renal tubules, thereby promoting renal accumulation and reducing background interference. Impressively, PS‐QRC allows noninvasive real‐time imaging of cisplatin‐induced AKI in mice as early as 12 h, significantly earlier than conventional serum biochemical and histopathological analyses. Furthermore, a high‐throughput screening platform was established using this nanoprobe to evaluate natural products, from which chrysin was identified as a promising renoprotective agent. Chrysin demonstrated both in vitro and in vivo renoprotective effects, with efficacy comparable to the established antioxidant N‐acetylcysteine. Moreover, PS‐QRC enabled quantitative monitoring of chrysin's dose‐dependent therapeutic response. Overall, this integrated probe provides a sensitive and reliable tool for early AKI diagnosis and the high‐throughput discovery of novel renoprotective drugs.
SN  - 2198-3844
ER  -