2. Academic Validation
  3. Selective targeting of coagulation factor X Gla domain by negatively charged gold nanoparticles: a novel method for controlled antithrombotic therapy

Selective targeting of coagulation factor X Gla domain by negatively charged gold nanoparticles: a novel method for controlled antithrombotic therapy

  • Mater Today Bio. 2025 Oct 1:35:102378. doi: 10.1016/j.mtbio.2025.102378.
Shixin Li 1,  Yuye Yin 1,  Dongmei Hou 1,  Yongchao Jin 1,  Yuan Zhao 1,  Jiangbo Tong 1,  Xu Liu 2,  Guomin Shen 3,  Tongtao Yue 4 5,  Kang Liu 1,  Yi Gu 1,  Luju Chen 1,  Fangzhe Ren 1 6,  Jinlin Huang 1 6,  Jian-Ke Tie 7,  Zhenyu Hao 1 8
Affiliations

Affiliations

  • 1 College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, 225009, China.
  • 2 College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, 225009, China.
  • 3 Department of Cell Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin, 150081, China.
  • 4 Institute of Coastal Environmental Pollution Control, Key Laboratory of Marine Environment and Ecology, Ministry of Education, Ocean University of China, Qingdao, Shandong, 266100, China.
  • 5 Laboratory for Marine Ecology and Environmental Science, Qingdao National Laboratory for Marine Science and Technology, Qingdao, Shandong, 266237, China.
  • 6 Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education of China, Yangzhou, Jiangsu, 225009, China.
  • 7 Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
  • 8 Affiliated Hospital, Yangzhou University, Yangzhou, Jiangsu, 225009, China.
PMID: 41111485 DOI: 10.1016/j.mtbio.2025.102378
Abstract

Venous thromboembolism (VTE) presents a significant global health burden due to its high incidence and potentially life-threatening complications. Although anticoagulants targeting vitamin K-dependent (VKD) factors, particularly factor X (FX), are widely employed, their efficacy is often limited by bleeding risks arising from off-target effects. Nanoparticle-based strategies, by contrast, enable precise and tunable modulation of protein activity through controlled adjustments in particle size, charge, and functionalization. In this work, we engineered negatively charged gold nanoparticles (GNPs) of defined sizes to selectively interact with the γ-carboxyglutamic acid (Gla) domain of VKD coagulation proteins. Using computational simulations, we systematically compared their binding conformations and affinities between GNPs and diverse VKD coagulation proteins, uncovering a size-dependent binding mechanism. This finding was subsequently validated through biochemical assays at both the molecular and cellular levels. Notably, GNPs with diameters of 2-3 nm demonstrated significantly higher affinity for FX compared to Other VKD proteins, such as factor IX and protein C. This specific binding triggered substantial conformational changes in FX, diminishing its membrane-binding affinity. These structural alterations also reduced its enzymatic activity and impaired its activation efficiency within the coagulation cascade, thereby effectively attenuating the cascade by selectively modulating FX activity. Comprehensive in vitro coagulation assays and in vivo murine thrombosis models further validated that GNP treatment effectively prolonged coagulation time, demonstrating robust antithrombotic efficacy. Collectively, our results establish a novel nanoparticle-based therapeutic paradigm for targeting FX, offering an innovative and promising approach for enhancing the safety and efficacy of VTE prevention and management.

Keywords

Antithrombotic strategy; Coagulation factor X; Gla domain; Venous thromboembolism.

Figures
Products