2. Academic Validation
  3. Carboxyl PEGylation of magnetic nanoparticles as antithrombotic and thrombolytic agents by calcium binding

Carboxyl PEGylation of magnetic nanoparticles as antithrombotic and thrombolytic agents by calcium binding

  • J Colloid Interface Sci. 2023 May 15:638:672-685. doi: 10.1016/j.jcis.2023.01.129.
Yingxin Bian 1,  Danhong Song 1,  Zejun Fu 2,  Chao Jiang 3,  Chen Xu 2,  Lei Zhang 4,  Kun Wang 5,  Shujun Wang 6,  Dongping Sun 7
Affiliations

Affiliations

  • 1 Institute of Chemicobiology and Functional Materials, School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, 200 Xiao Ling Wei, Nanjing 210094, China.
  • 2 Department of Physiology and Pathophysiology, Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
  • 3 School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, 200 Xiao Ling Wei, Nanjing 210094, China.
  • 4 Institute of Chemicobiology and Functional Materials, School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, 200 Xiao Ling Wei, Nanjing 210094, China. Electronic address: leizhang@njust.edu.cn.
  • 5 School of Pharmaceutical Sciences, Wenzhou Medical College, University Town, Chashan, Wenzhou 325035, China. Electronic address: wangkun@wmu.edu.cn.
  • 6 Department of Blood Transfusion, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China. Electronic address: shujun0106@sina.com.
  • 7 Institute of Chemicobiology and Functional Materials, School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, 200 Xiao Ling Wei, Nanjing 210094, China. Electronic address: sundpe301@163.com.
PMID: 36780849 DOI: 10.1016/j.jcis.2023.01.129
Abstract

Known to be biocompatible and hemocompatible, polyethylene glycol (PEG) has been widely used as anti-fouling coating of biomaterials. Nanoparticles coated with functionalized PEG were also investigated for their nano-cell interactions, but seldomly on the coagulation system, especially with platelets. Both experiments and molecular dynamic simulations indicate that terminal carboxylation of PEG promotes its binding with calcium, especially in the ionized form, which makes it potential anticoagulants. Further, the carboxyl PEGylated magnetic nanoparticle (HOOC-PEG2000-MNP) exhibits significantly increased anticoagulant and antiplatelet properties, by entering the open canalicular system (OCS) of human platelets and binding with the cytoplasmic calcium ions. HOOC-PEG2000-MNP also acts as effective thrombolytic agents in dissolving mature blood clots under oscillating magnetic field both in vitro and in vivo. Therefore, the carboxyl PEGylated magnetic nanoparticles are prototype agents for antithrombotic and thrombolytic therapies and provide a versatile platform for targeted and effective treatments of acute cardiovascular diseases.

Keywords

Anticoagulation; Calcium binding; Magnetic nanoparticles; Platelets; Thrombolysis.

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