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 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.

Oscillating Magnetic Field Regulates Cell Adherence and Endothelialization Based on Magnetic Nanoparticle-Modified Bacterial Cellulose.

Despite the widely explored biomaterial scaffolds in vascular tissue engineering applications lately, no ideal platform has been provided for small diameter synthetic vascular grafts mainly due to the thrombosis issue. Endothelium is the only known completely non-thrombogenic material; so, functional endothelialization onto vascular biomaterials is critical in maintaining the patency of vascular networks. Bacterial cellulose (BC) is a natural biomaterial with superior biocompatibility and appropriate hydrophilicity as potential vascular grafts. In previous studies, surface modification of active peptides such as Arg-Gly-Asp (RGD) sequences onto biomaterials has been proven to achieve accelerated and selective endothelial cell (EC) adhesion. In our study, we demonstrated a new strategy to remotely regulate the adhesion of endothelial cells based on an oscillating magnetic field and achieve successful endothelialization on the modified BC membranes. In details, we synthesized bacterial cellulose (BC), magnetic BC (MBC), and RGD peptide-grafted magnetic BC (RMBC), modified with the HOOC-PEG-COOH-coated iron oxide nanoparticles (PEG-IONs). The endothelial cells were cultured on the three materials under different frequencies of an oscillating magnetic field, including "stationary" (0 Hz), "slow" (0.1 Hz), and "fast" (2 Hz) groups. Compared to BC and MBC membranes, the cells on RMBC membranes generally show better adhesion and proliferation. Meanwhile, the "slow" frequency of a magnetic field promotes this phenomenon on RMBC and achieves endothelialization after culture for 4 days, whereas "fast" inhibits the cellular attachment. Overall, we demonstrate a non-invasive and convenient method to regulate the endothelialization process, with promising applications in vascular tissue engineering.