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

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 effec-tive 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.(c) 2023 Elsevier Inc. All rights reserved.

Automated summary

Polyethylene glycol (PEG), known for its biocompatibility and hemocompatibility, is widely used as an anti-fouling coating for biomaterials. Functionalized PEG-coated nanoparticles have been studied for their interactions with cells, but there is limited research on their effects on the coagulation system, particularly platelets. Experiments and molecular dynamic simulations have shown that carboxylation of PEG enhances its binding with calcium, making it a potential anticoagulant. Carboxyl PEGylated magnetic nanoparticles have shown increased anticoagulant and antiplatelet properties, and have the potential to be used for targeted and effective treatments of acute cardiovascular diseases.