An anticoagulant activity and protein interaction study of chondroitin sulfate-coated magnetic nanocomposites

Intravascular thrombosis is a significant cause of morbidity and mortality worldwide, highlighting the need for safe and effective anticoagulants. Chondroitin sulfate (CSul) has a weaker antithrombotic effect than heparin, but has a significantly lower bleeding risk, making it an attractive anticoagulant for the next generation of therapeutics. Here, we report for the first time the development of magnetically responsive anticoagulant nanocomposites prepared by functionalizing CSul on the surface of iron oxide magnetic nanoparticles (MNPs). The iron oxide MNPs were prepared by co-precipitation, and then functionalized with CSul at an elevated temperature to add the negatively charged functional groups that exhibit anticoagulant potential. Comprehensive physicochemical characterization, including transmission and scanning electron microscopy, X-ray diffraction, attenuated total reflectance Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, zeta potential as a function of pH, dynamic light scattering, thermogravimetry, and magnetometry, confirmed the presence of the CSul coating on the MNPs. The stability of the CSul coating was determined at physiologically relevant pH values, which revealed minor desorption of the polysaccharides. The hemocompatibility was investigated using the activated partial thromboplastin time and solid-liquid interaction tests with a key coagulation protein, i.e., bovine fibrinogen. The hemocompatibility studies showed that the MNPs@CSul prolonged clotting time compared to bare MNPs and exhibited reduced fibrinogen adsorption, consistent with partial anticoagulant and antifouling properties. Overall, these findings establish proof-of-concept that CSul-coated MNPs combine anticoagulant activity with magnetic manipulability. This dual functionality underlines their potential as a platform for externally guided antithrombotic therapies with a lower risk of bleeding.