RESUMO
Blood clotting disorders consisting of unwanted blood clot formation or excessive bleeding are some of the main causes of death worldwide. However, there are significant limitations in the current methods used to clinically monitor the dynamics of clot formation in human whole blood ex vivo. Here a new magnetic coagulometry platform for testing ex vivo coagulation is described. This platform exploits the sensitivity of the out-of-phase component of alternating current (AC) magnetic susceptibility (χ'') to variations in mobility and agglomeration of magnetic nanoparticles when trapped during blood clot formation. By labelling human whole blood with magnetic nanoparticles, the out-of-phase component of AC magnetic susceptibility shows that the dynamics of blood clot formation correlates with a decrease in the out-of-phase component χ'' over time activation of coagulation. This is caused by a rapid immobilisation of nanoparticles upon blood coagulation and compaction. In contrast, this rapid fall in the out-of-phase component χ'' is significantly slowed down when blood is pre-treated with three different anticoagulant drugs. Remarkably, the system showed sensitivity towards the effect of clinically used direct oral anticoagulation (DOAC) drugs in whole blood coagulation, in contrast to the inability of clinical routine tests prothrombin time (PT) and partial thromboplastin time (PTT) to efficiently monitor this effect. Translation of this nanomagnetic approach into clinic can provide a superior method for monitoring blood coagulation and improve the efficiency of the current diagnostic techniques.
Assuntos
Coagulação Sanguínea , Trombose , Humanos , Coagulação Sanguínea/fisiologia , Testes de Coagulação Sanguínea/métodos , Tempo de Protrombina , Fenômenos MagnéticosRESUMO
Metal alloy nanoparticles, and, in particular, permalloy, still hold an untapped potential in nanotechnology, although their poor stability against oxidation due to environmental exposure limits their use in many technological applications, and even more in life sciences. We propose a scalable single-step microwave-assisted method to produce water suspensions of Ni1-xFex nanoparticles without the need for an inert atmosphere, either organic solvents or any type of post-processing. We use hydrazine as a reducer, iron(II), iron(III) and nickel(II) chloride as precursors, 1,12-dodecanediol as a surfactant and water as a reaction medium. The mixture is heated at 160 °C for 10 minutes to obtain uniform alloy nanoparticles with sizes of around 24.5 nm for Ni (0% Fe) and 5.5 nm for 35% Fe that are forming uniform aggregates with sizes between 200 nm for Ni and 65 nm for iron oxide NPs. A linear increase of saturation magnetization is observed with an Fe content of up to 25%, whereas for larger percentages a sudden drop takes place due to the formation of iron oxides. X-ray diffraction measurements rule out the formation of any oxides after more than one year of storage at 4 °C, surely due to the presence of 1,12-dodecanediol at the surface, as evidenced by infrared spectroscopy.
RESUMO
The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia.
