Copper‐Doped Prussian Blue Nanozymes With Hyaluronic Acid‐Mediated Targeting Alleviate Oxidative Stress and Regulate Cholesterol Handling for Atherosclerosis Therapy
10 affiliations
- 1Department of Radiology Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital Shanghai People's Republic of China
- 2Department of Anesthesiology Changzheng Hospital Naval Medical University Shanghai People's Republic of China
- 3College of Chemistry and Materials Science Shanghai Normal University Shanghai People's Republic of China
- 4Wuhan United Imaging Life Science Instruments Ltd. Wuhan People's Republic of China
- 5Faculty of Medical Imaging Technology College of Health Science and Technology Shanghai Jiao Tong University School of Medicine Shanghai People's Republic of China
- 6Shanghai Normal University College of Life Science Shanghai People's Republic of China
- 7Key Laboratory of Multi‐Cell Systems Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Center for Excellence in Molecular Cell Science University of the Chinese Academy of Sciences Chinese Academy of Sciences Shanghai People's Republic of China
- 8Department of Pharmacy School of Medicine Renji Hospital Shanghai Jiao Tong University Shanghai People's Republic of China
- 9Department of Ultrasound in Medicine Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital Shanghai People's Republic of China
- 10Department of Nutrition and Food Hygiene School of Public Health Southeast University Nanjing People's Republic of China
Abstract
Atherosclerosis is driven by the persistent crosstalk among chronic inflammation, oxidative stress, and lipid dysmetabolism, largely orchestrated by plaque‐resident macrophages. However, therapeutic strategies capable of simultaneously modulating these interconnected pathological processes are still limited. Herein, we developed a hyaluronic acid‐coated, copper‐doped Prussian blue nanozyme (CuPB@HA) as a CD44‐associated plaque‐targeted nanotherapeutic. Guided by transcriptomic evidence of CD44 enrichment in atherosclerotic plaque macrophages, HA was incorporated to enhance lesion targeting and cellular internalization. In ox‐LDL‐stimulated macrophages, CuPB@HA effectively alleviated oxidative stress, suppressed inflammation, and attenuated lipid accumulation. Mechanistically, it reduced CD36‐dependent lipid uptake and increased the expression of cholesterol‐efflux‐related transporters ABCA1 and ABCG1, thereby shifting macrophages away from a pro‐inflammatory phenotype. In vivo, CuPB@HA preferentially accumulated within atherosclerotic lesions of ApoE−/− mice, significantly reducing plaque burden and improving plaque stability‐associated histological features. Collectively, CuPB@HA integrates redox regulation, macrophage lipid‐handling modulation, and inflammation attenuation, highlighting its potential as a targeted therapeutic strategy for atherosclerosis.
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BibTeX
@article{ou2026copperdoped,
title = {{Copper‐Doped Prussian Blue Nanozymes With Hyaluronic Acid‐Mediated Targeting Alleviate Oxidative Stress and Regulate Cholesterol Handling for Atherosclerosis Therapy}},
author = {Jianliang Ou and Ruihua Ji and Qinglu Zang and Mingkang Wang and Lingling Zhou and Yingliang Wei and Di Yang and Yue Wu and Hongxu Zhu and Jianrong Wu and Xiaojun Cai and Wenxian Du and Junjie Cheng and An Zeng and Yuehua Li},
journal = {Advanced Science},
year = {2026},
month = aug,
doi = {10.1002/advs.76976},
url = {https://doi.org/10.1002/advs.76976},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Copper‐Doped Prussian Blue Nanozymes With Hyaluronic Acid‐Mediated Targeting Alleviate Oxidative Stress and Regulate Cholesterol Handling for Atherosclerosis Therapy
AU - Jianliang Ou
AU - Ruihua Ji
AU - Qinglu Zang
AU - Mingkang Wang
AU - Lingling Zhou
AU - Yingliang Wei
AU - Di Yang
AU - Yue Wu
AU - Hongxu Zhu
AU - Jianrong Wu
AU - Xiaojun Cai
AU - Wenxian Du
AU - Junjie Cheng
AU - An Zeng
AU - Yuehua Li
PY - 2026
DA - 2026/08/05
JO - Advanced Science
DO - 10.1002/advs.76976
UR - https://doi.org/10.1002/advs.76976
AB - Atherosclerosis is driven by the persistent crosstalk among chronic inflammation, oxidative stress, and lipid dysmetabolism, largely orchestrated by plaque‐resident macrophages. However, therapeutic strategies capable of simultaneously modulating these interconnected pathological processes are still limited. Herein, we developed a hyaluronic acid‐coated, copper‐doped Prussian blue nanozyme (CuPB@HA) as a CD44‐associated plaque‐targeted nanotherapeutic. Guided by transcriptomic evidence of CD44 enrichment in atherosclerotic plaque macrophages, HA was incorporated to enhance lesion targeting and cellular internalization. In ox‐LDL‐stimulated macrophages, CuPB@HA effectively alleviated oxidative stress, suppressed inflammation, and attenuated lipid accumulation. Mechanistically, it reduced CD36‐dependent lipid uptake and increased the expression of cholesterol‐efflux‐related transporters ABCA1 and ABCG1, thereby shifting macrophages away from a pro‐inflammatory phenotype. In vivo, CuPB@HA preferentially accumulated within atherosclerotic lesions of ApoE−/− mice, significantly reducing plaque burden and improving plaque stability‐associated histological features. Collectively, CuPB@HA integrates redox regulation, macrophage lipid‐handling modulation, and inflammation attenuation, highlighting its potential as a targeted therapeutic strategy for atherosclerosis.
SN - 2198-3844
ER -