Mortality and disabilities as outcomes of cardiovascular diseases are primarily related to blood clotting. Optimization of thrombolytic drugs is aimed at the prevention of side effects (in particular, bleeding) associated with a disbalance between coagulation and anticoagulation caused by systemically administered agents. Minimally invasive and efficient approaches to deliver the thrombolytic agent to the site of clot formation are needed. Herein, we report a novel nanocomposite prepared by heparin-mediated cross-linking of urokinase with magnetite nanoparticles (MNPs@uPA). We showed that heparin within the composition evoked no inhibitory effects on urokinase activity. Importantly, the magneto-control further increased the thrombolytic efficacy of the composition. Using our nanocomposition, we demonstrated efficient lysis of experimental clots in vitro and in animal vessels followed by complete restoration of blood flow. No sustained toxicity or hemorrhagic complications were registered in rats and rabbits after single bolus i.v. injection of therapeutic doses of MNPs@uPA. We conclude that MNPs@uPA is a prototype of easy-to-prepare, inexpensive, biocompatible, and noninvasive thrombolytic nanomedicines potentially useful in the treatment of blood clotting.

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Magnetically controlled enzymatic composites have received much attention for both therapeutic and industrial applications. Until now, such materials have been composed of at least four components: the enzyme, magnetic nanoparticles, their stabilizing components, and an organic or inorganic (or hybrid) matrix as a carrier. However, such compositions affect the magnetic response and the enzymatic activity, and also pose obstacles for intravenous administration, because of regulatory restrictions. Here, we present a methodology for the creation of magnetic bioactive nanocomposites composed of only two biocompatible components: an enzyme and magnetite nanoparticles. A series of magnetic biocomposites with a full set of therapeutical and industrial proteins (carbonic anhydrase, ovalbumin, horseradish peroxidase, acid phosphatase, proteinase, and xylanase) were successfully created by the direct entrapment of the proteins within a sol–gel magnetite matrix specially developed for these aims. The activity of the entrapped enzymes was studied at different temperatures and concentrations, and it was found that they showed remarkable thermal stabilization induced by the ferria matrix. For instance, entrapped carbonic anhydrase catalyzed the decomposition of p-nitrophenylacetate at a temperature of 90 °C, while free enzyme completely loses activity and denaturates already at 70 °C. Magnetic characterization of the obtained biomaterials is provided.

Bleeding remains one of the main causes of premature mortality at present, with internal bleeding being the most dangerous case. In this paper, magnetic hemostatic nanoparticles are shown for the first time to assist in minimally invasive treatment of internal bleeding, implying the introduction directly into the circulatory system followed by localization in the bleeding zone due to the application of an external magnetic field. Nanoparticles were produced by entrapping human thrombin (THR) into a sol-gel derived magnetite matrix followed by grinding to sizes below 200 nm and subsequent colloidization. Prepared colloids show protrombotic activity and cause plasma coagulation in in vitro experiments. We also show here using a model blood vessel that the THR@ferria composite does not cause systematic thrombosis due to low activity, but being concentrated by an external magnetic field with simultaneous fibrinogen injection accelerates local hemostasis and stops the bleeding. For instance, a model vessel system with circulating blood at the puncture of the vessel wall and the application of a permanent magnetic field yielded a hemostasis time by a factor of 6.5 shorter than that observed for the control sample. Biocompatibility of composites was tested on HELF and HeLa cells and revealed no toxic effects.

A magnetite-only hydrogel was prepared for the first time by weak base mediated gelation of stable magnetite hydrosols at room temperature. The hydrogel consists of 10 nm magnetite nanoparticles linked by interparticle Fe-O-Fe bonds and has the appearance of a dark-brown viscous thixotropic material. The water content in the hydrogel could be up to 93.6% by mass while volume fraction reaches 99%. The material shows excellent biocompatibility and minor cytotoxic effects at concentrations up to 207 μg mL. The gel shows excellent sorption capacity for heavy metal adsorption such as chrome and lead ions, which is 225% more than the adsorption capacity of magnetite nanoparticles. Due to thixotropic nature, the gel demonstrates mechanical stimuli-responsive release behavior with up to 98% release triggered by ultrasound irradiation. The material shows superparamagnetic behavior with a coercivity of 65 emu g at 6000 Oe. The magnetite gels prepared could be used for the production of magnetite aerogels, magnetic drug delivery systems with controlled release and highly efficient sorbents for hydrometallurgy.