Suchergebnisse

Medial vascular calcification (MVC) is a degenerative process that involves the deposition of calcium in the arteries, with a high prevalence in chronic kidney disease (CKD), diabetes, and aging. Calcification is the process of precipitation largely of calcium phosphate, governed by the laws of thermodynamics that should be acknowledged in studies of this disease. Amorphous calcium phosphate (ACP) is the key constituent of early calcifications, mainly composed of Ca2+ and PO43– ions, which over time transform into hydroxyapatite (HAP) crystals. The supersaturation of ACP related to Ca2+ and PO43– activities establishes the risk of MVC, which can be modulated by the presence of promoter and inhibitor biomolecules. According to the thermodynamic parameters, the process of MVC implies: (i) an increase in Ca2+ and PO43– activities (rather than concentrations) exceeding the solubility product at the precipitating sites in the media; (ii) focally impaired equilibrium between promoter and inhibitor biomolecules; and (iii) the progression of HAP crystallization associated with nominal irreversibility of the process, even when the levels of Ca2+ and PO43– ions return to normal. Thus, physical-chemical processes in the media are fundamental to understanding MVC and represent the most critical factor for treatments' considerations. Any pathogenetical proposal must therefore comply with the laws of thermodynamics and their expression within the medial layer. ; This work was supported by a grant from the Ministry of Economy and Competitiveness, code PGC2018-098635-B-I00. Financial support from the European Union's Horizon 2020 FET Open Program (grants nos: 801305 and 829162), from the Spanish Ministry of Science, Innovation, and Universities (grant no: PGC2018_095795_B_I00), and from the Regional Government of Aragón (E11/17R) is also gratefully acknowledged. ; Peer reviewed

In this work we are studying whether calcium phosphate deposition (CPD) during vascular calcification is a passive or a cell-mediated mechanism. Passive CPD was studied in fixed vascular smooth muscle cells (VSMC), which calcify faster than live cells in the presence of 1.8 mM Ca2+ and 2 mM P i. CPD seems to be a cell-independent process that depends on the concentration of calcium, phosphate, and hydroxyl ions, but not on Ca X P i concentration products, given that deposition is obtained with 2 X 2 and 4 X 1 Ca X Pi mM2 but not with 2 X 1 or 1 X 4 Ca X Pi mM2. Incubation with 4 mM Pi without CPD (i.e., plus 1 mM Ca) does not induce osteogene expression. Increased expression of bone markers such as Bmp2 and Cbfa1 is only observed concomitantly with CPD. Hydroxyapatite is the only crystalline phase in both lysed and live cells. Lysed cell deposits are highly crystalline, whereas live cell deposits still contain large amounts of amorphous calcium. High-resolution transmission electron microscopy revealed a nanostructure of rounded crystallites of 5-10 nm oriented at random in lysed cells, which is compatible with spontaneous precipitation. The nanostructure in live cells consisted of long fiber crystals, 10-nm thick, embedded in an amorphous matrix. This structure indicates an active role of cells in the process of hydroxyapatite crystallization. In conclusion, our data suggest that CPD is a passive phenomenon, which triggers the osteogenic changes that are involved in the formation of a well organized, calcified crystalline structure. Copyright © 2011 the American Physiological Society. ; This work was supported by a grant from the Spanish Ministry of Science and Innovation (BFU2009-12763/BFI to V. Sorribas), research grant MAT2007-61621 from the Spanish CICYT Project Consolider-Ingenio in Molecular Nanoscience CSD2007-00010 from the Spanish Ministry of Science, and a predoctoral fellowship from the Government of Aragón, Spain (B086/2007 to R. Villa-Bellosta). ; Peer Reviewed

Wireless actuation at the nanoscale is vital in many contexts, and magnetic fields acting on nanoparticles (NPs) are among the most effective tools when actuation concerns linear forces. However, effective tools to apply torques at the nanoscale are still missing, because NPs where the magnetic moment is strongly coupled to the lattice agglomerate due to their high magnetic moment. Here, we show that gallium-doped ε-iron oxide NPs have small interparticle magnetic interactions and huge lattice-coupling for efficiently applying torques at the nanoscale. In this view, they are expected to be useful tools to efficiently apply mechanical forces to induce cellular apoptosis and to discern between mechanical and thermal contributions to cellular apoptosis currently under debate. ; Financial support by European Union's Horizon 2020 FET Open program [Grants no: 801305 and 829162] Spanish Ministry of Science Innovation and Universities [Grant no: PGC2018_095795_B_I00], Diputación General de Aragón [E11/17R], FCT/MEC and co-financed by FEDER [Grants no: P2020-PTDC/CTMNAN-4511-2014, UIDB/50011/2020 and UIDP/50011/2020] and support of the publication fee by the CSIC Open Access Publication Support Initiative (URICI) are gratefully acknowledged. Authors would like to acknowledge the use of Servicio General de Apoyo a la Investigación-SAI, Universidad de Zaragoza. ; Support of the publication fee by the CSIC Open Access Publication Support Initiative (URICI). ; Peer reviewed

Measurement of thermogenesis in individual cells is a remarkable challenge due to the complexity of the biochemical environment (such as pH and ionic strength) and to the rapid and yet not well-understood heat transfer mechanisms throughout the cell. Here, we present a unique system for intracellular temperature mapping in a fluorescence microscope (uncertainty of 0.2 K) using rationally designed luminescent Ln3+-bearing polymeric micellar probes (Ln = Sm, Eu) incubated in breast cancer MDA-MB468 cells. Two-dimensional (2D) thermal images recorded increasing the temperature of the cells culture medium between 296 and 304 K shows inhomogeneous intracellular temperature progressions up to ∼20 degrees and subcellular gradients of ∼5 degrees between the nucleolus and the rest of the cell, illustrating the thermogenic activity of the different organelles and highlighting the potential of this tool to study intracellular processes. ; This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 and UIDP/50011/2020, financed by Portuguese funds through the FCT/MEC and when appropriate cofinanced by FEDER under the PT2020 Partnership Agreement. Financial support from the project (NanoHeatControl, POCI-01-0145-FEDER-031469), funded by FEDER, through POCI and by Portuguese funds (OE), through FCT/MCTES, by European Union's Horizon 2020 FET Open program under grant agreement nos. 801305 and 829162, Spanish Ministry of Science Innovation and Universities (grant no: PGC2018_095795_B_I00) and Diputación General de Aragón (E11/17R) are acknowledged. ANCN thanks SusPhotoSolutions project, CENTRO-01-0145-FEDER-000005, Portugal, for his grant. The authors acknowledge the use of Servicio General de Apoyo a la Investigación-SAI, Universidad de Zaragoza. ; Peer reviewed

Biocompatibility restrictions have limited the use of magnetic nanoparticles for magnetic hyperthermia therapy to iron oxides, namely magnetite (Fe3O4) and maghemite (γ-Fe2O3). However, there is yet another magnetic iron oxide phase that has not been considered so far, in spite of its unique magnetic properties: ε-Fe2O3. Indeed, whereas Fe3O4 and γ-Fe2O3 have a relatively low magnetic coercivity, ε-Fe2O3 exhibits a giant coercivity. In this report, the heating power of ε-Fe2O3 nanoparticles in comparison with γ-Fe2O3 nanoparticles of similar size (∼20 nm) was measured in a wide range of field frequencies and amplitudes, in uncoated and polymer-coated samples. It was found that ε-Fe2O3 nanoparticles primarily heat in the low-frequency regime (20–100 kHz) in media whose viscosity is similar to that of cell cytoplasm. In contrast, γ-Fe2O3 nanoparticles heat more effectively in the high frequency range (400–900 kHz). Cell culture experiments exhibited no toxicity in a wide range of nanoparticle concentrations and a high internalization rate. In conclusion, the performance of ε-Fe2O3 nanoparticles is slightly inferior to that of γ-Fe2O3 nanoparticles in human magnetic hyperthermia applications. However, these ε-Fe2O3 nanoparticles open the way for switchable magnetic heating owing to their distinct response to frequency. ; This work was supported by European Union's Horizon 2020 FET Open program [Grants no: 801305 and 829162] Spanish Ministry of Science Innovation and Universities [Grant no: PGC2018_095795_B_I00] and Diputación General de Aragón [E11/17R]. Authors would like to acknowledge the use of Servicio General de Apoyo a la Investigación-SAI, Universidad de Zaragoza. This work was developed within the scope of the projects CoolPoint P2020-PTDC-CTMNAN-4511-2014 and CICECO-Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the FCT/MEC and co-financed by FEDER under the PT2020 Partnership Agreement. ; We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI). ; Peer reviewed

This article belongs to the Special Issue Magnetic Nanoparticles as High-Frequency Nano-Heater. ; 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. ; This work was supported by the NoCanTher project, which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 685795. The authors acknowledge support from the COST Association through the COST actions "RADIOMAG" (TD1402) and "MyWAVE" (CA17115). D.O., A.S.-O. and I.R.-R. acknowledge financial support from the Community of Madrid under Contracts No. PEJD-2017-PRE/IND-3663 and PEJ-2018-AI/IND-11069, from the Spanish Ministry of Science through the Ramón y Cajal grant RYC2018-025253-I and Research Networks RED2018-102626-T, as well as the Ministry of Economy and Competitiveness through the grants MAT2017-85617-R, MAT2017-88148R and the "Severo Ochoa" Program for Centers of Excellence in R&D (SEV-2016-0686). M.B. and N.T.K.T. would like to thank EPSRC for funding (grant EP/K038656/1 and EP/M015157/1) and AOARD (FA2386-17-1-4042) award. This work was additionally supported by the EMPIR program co-financed by the Participating States and from the European Union's Horizon 2020 research and innovation program, grant no. 16NRM04 "MagNaStand". The work was further supported by the DFG grant CRC "Matrix in Vision" (SFB 1340/1 2018, no 372486779, project A02). ; Peer reviewed

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. ; This work was supported by the NoCanTher project, which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 685795. The authors acknowledge support from the COST Association through the COST actions "RADIOMAG" (TD1402) and "MyWAVE" (CA17115). D.O., A.S.-O. and I.R.-R. acknowledge financial support from the Community of Madrid under Contracts No. PEJD-2017-PRE/IND-3663 and PEJ-2018-AI/IND-11069, from the Spanish Ministry of Science through the Ramon y Cajal grant RYC2018-025253-I and Research Networks RED2018-102626-T, as well as the Ministry of Economy and Competitiveness through the grants MAT2017-85617-R, MAT2017-88148R and the "Severo Ochoa" Program for Centers of Excellence in R&D (SEV-2016-0686). M.B. and N.T.K.T. would like to thank EPSRC for funding (grant EP/K038656/1 and EP/M015157/1) and AOARD (FA2386-171-4042) award. This work was additionally supported by the EMPIR program co-financed by the Participating States and from the European Union's Horizon 2020 research and innovation program, grant no. 16NRM04 "MagNaStand". The work was further supported by the DFG grant CRC "Matrix in Vision" (SFB 1340/1 2018, no 372486779, project A02).