2. Academic Validation
  3. Prussian Blue Nanozyme Disrupts the Self-Reinforcing Loop of Tauopathy via Triple-Action Mechanism

Prussian Blue Nanozyme Disrupts the Self-Reinforcing Loop of Tauopathy via Triple-Action Mechanism

  • Adv Healthc Mater. 2026 Mar 9:e05286. doi: 10.1002/adhm.202505286.
Fei Wu 1 2 3 4,  Jiani Huang 2 3 4,  Jing Wang 2 3 4,  Rongrong Wu 5,  Hang Zhang 2 3 4,  Chentao Jin 1 2 3 4 6,  Cheng Chen 2 3 4,  Rui Zhou 1 2 3 4,  Peili Cen 2 3 4,  Liangfei Tian 7,  Yuanyi Zheng 5,  Xiaojun Cai 5,  Mei Tian 8,  Hong Zhang 1 2 3 4 6 7,  Yan Zhong 1 2 3 4 6
Affiliations

Affiliations

  • 1 Department of Nuclear Medicine, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China.
  • 2 Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
  • 3 Institute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, China.
  • 4 Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, China.
  • 5 Shanghai Key Laboratory of Neuro-Ultrasound for Diagnosis and Treatment, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 6 Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, China.
  • 7 College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China.
  • 8 Human Phenome Institute, Fudan University, Shanghai, China.
PMID: 41797478 DOI: 10.1002/adhm.202505286
Abstract

Tauopathies, such as Alzheimer's disease, are driven by a self-reinforcing pathological triad of tau aggregation, oxidative stress, and Autophagy dysfunction, which remains inadequately addressed by single-target therapies. Herein, we engineer an ultrasmall Prussian blue nanozyme (PBzyme) as a multienzyme-mimetic and multi-target agent to concurrently disrupt this vicious cycle. PBzyme functions as a potent tau fibril inhibitor, with molecular dynamics simulations revealing high-affinity binding to β-sheet domains (-400 kJ/mol), thereby reducing tau phosphorylation and hippocampal burden. In parallel, PBzyme acts as a multifunctional antioxidant enzyme mimic, efficiently neutralizing •OH, O2 -, and H2O2 to alleviate oxidative injury. Furthermore, PBzyme restores autophagic flux by activating AMPK/ULK1 signaling while inhibiting the mechanistic target of rapamycin (mTOR), thereby promoting the clearance of tau aggregates. In an okadaic acid-induced tauopathy rat model, PBzyme treatment effectively preserved synaptic integrity, suppressed neuroinflammation, mitigated neuronal loss, and rescued cognitive deficits. Notably, PBzyme enters cells to counteract intracellular tau and ROS, overcoming a key limitation of conventional biologics. This work establishes PBzyme as an integrated nanoagent offering a synergistic therapeutic strategy against tauopathies and Other ROS-related neurodegenerative diseases.

Keywords

Alzheimer's disease; cognitive impairment; nanozyme; prussian blue; tau pathology.

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