| 1. |
- Fortes Brollo, Maria Eugenia, et al.
(författare)
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Combined Magnetoliposome Formation and Drug Loading in One Step for Efficient Alternating Current-Magnetic Field Remote-Controlled Drug Release.
- 2020
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 12:4, s. 4295-4307
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Tidskriftsartikel (refereegranskat)abstract
- We have developed a reproducible and facile one step strategy for the synthesis of doxorubicin loaded magnetoliposomes by using a thin-layer evaporation method. Liposomes of around 200 nm were made of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and iron oxide nanoparticles (NPs) with negative, positive, and hydrophobic surfaces that were incorporated outside, inside, or between the lipid bilayers, respectively. To characterize how NPs are incorporated in liposomes, advanced cryoTEM and atomic force microscope (AFM) techniques have been used. It was observed that only when the NPs are attached outside the liposomes, the membrane integrity is preserved (lipid melt transition shifts to 38.7 °C with high enthalpy 34.8 J/g) avoiding the leakage of the encapsulated drug while having good colloidal properties and the best heating efficiency under an alternating magnetic field (AMF). These magnetoliposomes were tested with two cancer cell lines, MDA-MB-231 and HeLa cells. First, 100% of cellular uptake was achieved with a high cell survival (above 80%), which is preserved (83%) for doxorubicin-loaded magnetoliposomes. Then, we demonstrate that doxorubicin release can be triggered by remote control, using a noninvasive external AMF for 1 h, leading to a cell survival reduction of 20%. Magnetic field conditions of 202 kHz and 30 mT seem to be enough to produce an effective heating to avoid drug degradation. In conclusion, these drug-loaded magnetoliposomes prepared in one step could be used for drug release on demand at a specific time and place, efficiently using an external AMF to reduce or even eliminate side effects.
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| 2. |
- Corrales-Pérez, Belén, et al.
(författare)
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Alternative Metallic Fillers for the Preparation of Conductive Nanoinks for Sustainable Electronics
- 2024
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Ingår i: Advanced Functional Materials. - : John Wiley and Sons Inc. - 1616-301X .- 1616-3028.
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Tidskriftsartikel (refereegranskat)abstract
- The development of electronics with net zero carbon emissions through more efficient and environmentally friendly materials and processes is still a challenge. Here, alternative chemical synthesis routes of metal conductive nanoparticles, based on biodegradable materials are explored, such as nickel, iron–nickel alloy and iron nanoparticles, to be used, in the long term, as fillers in inks for inject printing. Thus, Ni and FeNi metal nanoparticles of 25–12 nm, forming aggregates of 614–574 nm, respectively, are synthesized in water in the presence of a polyol and a reducing agent and under microwave heating that enables a more uniform and fast heating. Iron nanoparticles of 120 ± 40 nm are synthesized in polyol that limits the aggregation and the oxidation degree. Commercial metal nanoparticles of iron and nickel, are coated with ethylene glycol and used for comparison. The conductivity of nanoparticles when pressed into pellets remains similar for both commercial and synthesized samples. However, when deposited on a strip line and heated, synthesized Ni, FeNi, and Fe nanoparticles show significant conductivity and interesting magnetic properties. It is demonstrated that the nanosize facilitates sintering at reduced temperatures and the capping agents prevent oxidation, resulting in promising conductive fillers for printed electronic applications.
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| 3. |
- Diez-Quijada, Leticia, et al.
(författare)
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In Vitro Toxicity Evaluation of Cyanotoxins Cylindrospermopsin and Microcystin-LR on Human Kidney HEK293 Cells
- 2022
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Ingår i: Toxins. - : MDPI. - 2072-6651. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- Cyanotoxins are secondary metabolites produced by different types of cyanobacteria. Among them, Cylindrospermopsin (CYN) and Microcystins (MCs) stand out due to their wide geographical distribution and toxicity in various organs, including the kidney, which is involved in their distribution and elimination. However, the renal toxicity caused by CYN and MCs has hardly been studied. The aim of this work was to assess the cytotoxicity effects caused by CYN and MC-LR in the renal cell line HEK293, and for the first time, the influence of CYN on the gene expression of selected genes in these cells by quantitative real-time PCR (qRT-PCR). CYN caused an upregulation in the gene expression after exposure to the highest concentration (5 mu g/mL) and the longest time of exposure (24 h). Moreover, shotgun proteomic analysis was used to assess the molecular responses of HEK293 cells after exposure to the individuals and combinations of CYN + MC-LR. The simultaneous exposure to both cyanotoxins caused a greater number of alterations in protein expression compared to single toxins, causing changes in the cellular, lipid and protein metabolism and in protein synthesis and transport. Further studies are needed to complete the toxicity molecular mechanisms of both CYN and MC-LR at the renal level.
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| 4. |
- Fortes Brollo, Maria Eugenia, et al.
(författare)
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Magnetic properties of nanoparticles as a function of their spatial distribution on liposomes and cells
- 2018
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 20:26, s. 17829-17838
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Tidskriftsartikel (refereegranskat)abstract
- The aggregation processes of magnetic nanoparticles in biosystems are analysed by comparing the magnetic properties of three systems with different spatial distributions of the nanoparticles. The first one is iron oxide nanoparticles (NPs) of 14 nm synthesized by coprecipitation with two coatings, (3-aminopropyl)trimethoxysilane (APS) and dimercaptosuccinic acid (DMSA). The second one is liposomes with encapsulated nanoparticles, which have different configurations depending on the NP coating (NPs attached to the liposome surface or encapsulated in its aqueous volume). The last system consists of two cell lines (Pan02 and Jurkat) incubated with the NPs. Dynamic magnetic behaviour (AC) was analysed in liquid samples, maintaining their colloidal properties, while quasi-static (DC) magnetic measurements were performed on lyophilised samples. AC measurements provide a direct method for determining the effect of the environment on the magnetization relaxation of nanoparticles. Thus, the imaginary (χ'') component shifts to lower frequencies as the aggregation state increases from free nanoparticles to those attached or embedded into liposomes in cell culture media and more pronounced when internalized by the cells. DC magnetization curves show no degradation of the NPs after interaction with biosystems in the analysed timescale. However, the blocking temperature is shifted to higher temperatures for the nanoparticles in contact with the cells, regardless of the location, the incubation time, the cell line and the nanoparticle coating, supporting AC susceptibility data. These results indicate that the simple fact of being in contact with the cells makes the nanoparticles aggregate in a non-controlled way, which is not the same kind of aggregation caused by the contact with the cell medium nor inside liposomes.
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| 5. |
- Santana-Otero, Antonio, et al.
(författare)
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Microwave-assisted NixFe1-x nanoclusters ultra-stable to oxidation in aqueous media
- 2022
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- 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 degrees 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 degrees C, surely due to the presence of 1,12-dodecanediol at the surface, as evidenced by infrared spectroscopy.
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| 6. |
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| 7. |
- Bogren, Sara, et al.
(författare)
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Classification of Magnetic Nanoparticle Systems—Synthesis, Standardization and Analysis Methods in the NanoMag Project
- 2015
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 16:9, s. 20308-20325
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Tidskriftsartikel (refereegranskat)abstract
- This study presents classification of different magnetic single- and multi-core particle systems using their measured dynamic magnetic properties together with their nanocrystal and particle sizes. The dynamic magnetic properties are measured with AC (dynamical) susceptometry and magnetorelaxometry and the size parameters are determined from electron microscopy and dynamic light scattering. Using these methods, we also show that the nanocrystal size and particle morphology determines the dynamic magnetic properties for both single- and multi-core particles. The presented results are obtained from the four year EU NMP FP7 project, NanoMag, which is focused on standardization of analysis methods for magnetic nanoparticles.
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| 8. |
- Caja, Laia, et al.
(författare)
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The protein kinase LKB1 promotes self-renewal and blocks invasiveness in glioblastoma
- 2022
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Ingår i: Journal of Cellular Physiology. - : John Wiley & Sons. - 0021-9541 .- 1097-4652. ; 237:1, s. 743-762
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Tidskriftsartikel (refereegranskat)abstract
- The role of liver kinase B1 (LKB1) in glioblastoma (GBM) development remains poorly understood. LKB1 may regulate GBM cell metabolism and has been suggested to promote glioma invasiveness. After analyzing LKB1 expression in GBM patient mRNA databases and in tumor tissue via multiparametric immunohistochemistry, we observed that LKB1 was localized and enriched in GBM tumor cells that co-expressed SOX2 and NESTIN stemness markers. Thus, LKB1-specific immunohistochemistry can potentially reveal subpopulations of stem-like cells, advancing GBM patient molecular pathology. We further analyzed the functions of LKB1 in patient-derived GBM cultures under defined serum-free conditions. Silencing of endogenous LKB1 impaired 3D-gliomasphere frequency and promoted GBM cell invasion in vitro and in the zebrafish collagenous tail after extravasation of circulating GBM cells. Moreover, loss of LKB1 function revealed mitochondrial dysfunction resulting in decreased ATP levels. Treatment with the clinically used drug metformin impaired 3D-gliomasphere formation and enhanced cytotoxicity induced by temozolomide, the primary chemotherapeutic drug against GBM. The IC50 of temozolomide in the GBM cultures was significantly decreased in the presence of metformin. This combinatorial effect was further enhanced after LKB1 silencing, which at least partially, was due to increased apoptosis. The expression of genes involved in the maintenance of tumor stemness, such as growth factors and their receptors, including members of the platelet-derived growth factor (PDGF) family, was suppressed after LKB1 silencing. The defect in gliomasphere growth caused by LKB1 silencing was bypassed after supplementing the cells with exogenous PFDGF-BB. Our data support the parallel roles of LKB1 in maintaining mitochondrial homeostasis, 3D-gliomasphere survival, and hindering migration in GBM. Thus, the natural loss of, or pharmacological interference with LKB1 function, may be associated with benefits in patient survival but could result in tumor spread.
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| 9. |
- Dadras, Mahsa Shahidi, et al.
(författare)
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The polarity protein Par3 coordinates positively self-renewal and negatively invasiveness in glioblastoma
- 2021
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Ingår i: Cell Death and Disease. - : Springer Nature. - 2041-4889. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma (GBM) is a brain malignancy characterized by invasiveness to the surrounding brain tissue and by stem-like cells, which propagate the tumor and may also regulate invasiveness. During brain development, polarity proteins, such as Par3, regulate asymmetric cell division of neuro-glial progenitors and neurite motility. We, therefore, studied the role of the Par3 protein (encoded by PARD3) in GBM. GBM patient transcriptomic data and patient-derived culture analysis indicated diverse levels of expression of PARD3 across and independent from subtypes. Multiplex immunolocalization in GBM tumors identified Par3 protein enrichment in SOX2-, CD133-, and NESTIN-positive (stem-like) cells. Analysis of GBM cultures of the three subtypes (proneural, classical, mesenchymal), revealed decreased gliomasphere forming capacity and enhanced invasiveness upon silencing Par3. GBM cultures with suppressed Par3 showed low expression of stemness (SOX2 and NESTIN) but higher expression of differentiation (GFAP) genes. Moreover, Par3 silencing reduced the expression of a set of genes encoding mitochondrial enzymes that generate ATP. Accordingly, silencing Par3 reduced ATP production and concomitantly increased reactive oxygen species. The latter was required for the enhanced migration observed upon silencing of Par3 as anti-oxidants blocked the enhanced migration. These findings support the notion that Par3 exerts homeostatic redox control, which could limit the tumor cell-derived pool of oxygen radicals, and thereby the tumorigenicity of GBM.
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| 10. |
- Gutiérrez, Lucía, et al.
(författare)
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Synthesis methods to prepare single- and multi-core iron oxide nanoparticles for biomedical applications
- 2015
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Ingår i: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9226 .- 1477-9234. ; 44:7, s. 2943-2952
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Tidskriftsartikel (refereegranskat)abstract
- We review current synthetic routes to magnetic iron oxide nanoparticles for biomedical applications. We classify the different approaches used depending on their ability to generate magnetic particles that are either single-core (containing only one magnetic core, i.e. a single domain nanocrystal) or multi-core (containing several magnetic cores, i.e. single domain nanocrystals). The synthesis of single-core magnetic nanoparticles requires the use of surfactants during the particle generation, and careful control of the particle coating to prevent aggregation. Special attention has to be paid to avoid the presence of any toxic reagents after the synthesis if biomedical applications are intended. Several approaches exist to obtain multi-core particles based on the coating of particle aggregates; nevertheless, the production of multi-core particles with good control of the number of magnetic cores per particle, and of the degree of polydispersity of the core sizes, is still a difficult task. The control of the structure of the particles is of great relevance for biomedical applications as it has a major influence on the magnetic properties of the materials.
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