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Resumen del trabajo presentado a la "2nd European Event in Nanoscience & Nanotechnology" celebrado en Bilbao (España) del 23 al 26 de abril de 2013., Working machinery in life is nanometric, thus, it is no wonder tliat the development of adequate nanotools would be very helpful in biomedical science. In this direction, the idea behind this work is to build a nanoplatform that can incorporate, in an easy way, multiple physical and biological functionalities. The core of the platform is an hydrophobic polymer that may be used as a matrix for the encapsulation of inorganic nanoparticles (magnetic, luminescent, radioactive, . . .). This matrix contains a Michael acceptor (or an acceptor) on its surface for functionalization. Organic bioactive molecules are attached to one end of a hydrophilic polymer (Le. PEG) terminated on a Michael acceptor (or a donor), and then they are anchored to the hydrophobic core by Michael addition. This system has the advantages of a clean synthesis (no by-products), mild conditions, and an easy and controlled multifunctionalization. The nanoplatform has been functionalized with radiochemical tracers (In111), luminescent dyes (fluorescein, rhodamine, lanthanide compounds), and magnetic nanoparticles, and therefore it can be a powerful tool in imaging. Besides, it has also been functionalized with a therapeutical drug, an antibody, and an optical thermometer made of lanthanide complexes. Health safety of tlhe system has been tested in cellular and in vivo assays. The nanoplatform is highly stable in biological fluids, shows low cell toxicity, high capacity of cell internalization, excellent hematocompatibility, and anticoagulation properties. It is shown that magnetic properties can be tuned up in the whole superparamagnetic range. Moreover, the system has shown excellent performance in magnetic resonance imaging and liyperthermia.

[Background]: Superparamagnetic iron oxide nanoparticles (SPIONs) are inorganic nanomaterials gaining strong clinical interest due to their increasing number of biological and medical applications. The stabilization of SPIONs in a biocompatible stable suspension (bioferrofluid) is generally achieved by an adequate polymeric coating. As many applications using these materials are intended for clinical use through intravenous injection, it is of outmost importance to evaluate heir hemostatic behaviour. [Objectives]: The aim of this work is to evaluate the hemocompatibility of selected polymer coated bioferrofluids and of their separated components by observing the effects of the bioferrofluid on: the coagulation process-by measuring the prothrombin time (PT) and activated partial thromboplastin time (aPTT)-, the complete blood count (CBC)-Erythrocytes, Leucocytes, Platelets, Hemoglobin and hematocrit-and the hemolysis. [Methods]: A SPIONs/bioferrofluid model consisting of a magnetic core of iron oxide nanoparticles embedded within poly(4-vinyl pyridine) (P4VP) and all coated with polyethylene glycol (PEG) has been selected. [Results and Conclusions]: By increasing the concentration of the bioferrofluids an inhibitory effect on the intrinsic pathway of blood coagulation is observed, as indicated by significant increase in aPTT in vitro while PT values stay normal. The effect of the coating components on the inhibition of blood coagulation process shows that PEG has no effect on the process while the P4VP-g-PEG copolymer coating has a strong anticoagulant effect indicating that P4VP is at the origin of such effects. The studied bioferrofluids have no effect on the CBC neither they show in vitro hemolytic effect on blood.

Trabajo presentado a la conferencia NanoSpain celebrada en Santander (España) del 27 de febrero al 1 de marzo de 2012.

Resumen del póster presentado a la: "13th edition of Trends in Nanotechnology International Conference" celebrada en Madrid (España) del 10 al 14 de septiembre de 2012.-- Pdf adjunto con las figuras., Superparamagnetic iron oxide nanoparticles (SPIONs) have been of great interest since the last decades due to their important contributions to nanomedicine. These inorganic nanomaterials can be useful as a diagnostic tool (e.g. magnetic resonance image contrast agent), a therapeutic tool (e.g. hyperthermia), or a theranostic tool. Stable biocompatible suspension of these nanoparticles is mandatory for efficient application, which is achieved by an adequate polymeric coating. Our model consists of iron oxide nanoparticles (ɣ-Fe2O3) embedded within a hydrophobic poly(vinylpyridine) (P4VP) polymer and coated with a hydrophilic polyethylene glycol (PEG). A fraction of coating PEG can also be functionalized for the conjugation of fluorescent dyes (dual reporter nanoparticles), antibodies and drugs Fig1. These nanoparticles are dispersed in phosphate buffer saline (PBS) at pH 7.4 to mimic physiological conditions. The resulting ferrofluids have core diameter (ferric oxide nanoparticles diameter) ranging between 4 to 15 nm, with 10% size dispersion, and hydrodynamic diameter ranging between 50 to 164 nm. Since the in vivo delivery of these nanoparticles for biomedical applications ends at the cell, studies pertaining to the toxicological effect on the cell (cytotoxicity), and nanoparticles cellular uptake and uptake kinetics are of utmost importance. Cytotoxicity studies of the ferrofluids have been carried out on two different cell lines, opossum kidney cells (OK) and vascular smooth muscle cells (VSMS). The activity of the lactate dehydrogenase in culture media was determined as a function of the dose. LC50 has been also calculated. As the nanoparticles uptake by the cell is depending on several factors, this work focused on the effect of the nanoparticle size and cell type on the cellular uptake. Sub cellular tracking studies have been carried out using fluorescent nanoparticles. Results show the localization of the nanoparticles after 24h of incubation with the cells inside the lysosomes Fig 2. By using the pharmacological inhibitor we found that the nanoparticles uptake takes place by clathrin-dependent endocytosis. These nanoparticles are developed for intravenous administration; therefore, studies pertaining to their haematological behaviour are of outmost importance and should be included in the toxicity and compatibility tests to be made in the development of these nanoparticles. We studied the effect of the nanoparticles and their polymers on the blood coagulation process. Results show that P4VPg-PEG-coated SPIONs in PBS act as non-specific circulating anticoagulant agents in vitro. While PEG component does not seem to have any effect on the coagulation process, the coating copolymer P4VP-g-PEG shows strong anticoagulant behaviour indicating that P4VP is at the origin of the effect.

Resumen del trabajo presentado a: "36th FEBS Congress, Biochemistry for Tomorrow's Medicine, Lingotto Conference Center, Torino, Italy, June 25-30, 2011".

La presente invención describe un procedimiento para el recubrimiento de nanopartículas para conseguir dispersiones estables de dichas partículas en un medio líquido y de su funcionalización superficial con grupos que poseen actividad física, como luminiscencia, actividad química, como capacidad catalítica, y/o actividad biológica, como capacidad de unión selectiva con un ente biológico., Consejo Superior de Investigaciones Científicas (España), A1 Solicitud de patente con informe sobre el estado de la técnica

[EN] The present invention relates to a method for coating nanoparticles to achieve stable dispersions of said particles in a liquid medium and the surface functionalization thereof with groups that have physical activity such as luminescence, chemical activity such as catalytic capacity and/or biological activity such as a capacity for selectively binding with a biological entity., [ES] La presente invención describe un procedimiento para el recubrimiento de nano partículas para conseguir dispersiones estables de dichas partículas en un medio líquido y de su funcionalizacion superficial con grupos que poseen actividad fIsica, como lmniniscencia, actividad química, como capacidad catalítica, y/o actividad biológica, como capacidad de unión selectiva con un ente biológico., Consejo Superior de Investigaciones Científicas, A1 Solicitud de patente con informe sobre el estado de la técnica