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Iron oxide nanoparticles (Fe

Analytical tests/devices that are used outside laboratory settings are required to have a very simple analytical protocol to get clearance by regulatory authorities. This study describes sink/float magnetic immunoassays, a new type of rapid, mix-and-observe, instrument-free tests for the detection of biomarkers in untreated biological samples that are very simple and might meet the simple-to-use criterion of authorities to be used in the field. These tests can tell whether an analyte is above or below a predetermined level within 25-45 minutes based on the sinking or floating of a mm-sized sphere on the surface of which an immunoassay that uses reporter antibodies conjugated to superparamagnetic nanoparticles is performed. This manuscript describes the theory and proof-of-concept applications of sink/float magnetic immunoassays for the detection of C-Reactive Protein, anti-Treponema pallidum antibodies and E. coli bacteria.

Poly(thioether-ester) (PTEe) nanoparticles obtained by thiol-ene polymerization have received attention of many researchers due to several advantages, including, biocompatibility and biodegradability. The search for new nanomaterials requires toxicity studies to assess potential toxic effects of their administration. Therefore, the aim of this study was to evaluate the in vivo acute toxicity of PTEe and poly(thioether-ester)-coated magnetic nanoparticles prepared by thiol-ene polymerization in miniemulsion. These nanoparticles presented a mean size of approximately 120 nm, spherical morphology, and negative surface charge. Doses of 40 mg/kg were administered intraperitoneally to Swiss mice and nociceptive, behavioral and biochemical parameters were investigated in five different organs. None of the nanoparticles led to any alterations in the nociceptive and behavioral responses. Biochemical alterations were observed in liver, decreasing the sulfhydryl and glutathione (GSH) levels, suggesting the dependence of the GSH metabolism in the elimination of the nanoparticles. In general, both nanoparticle types did not cause disturbances in biochemical parameters analyzed in others organs. These results suggest that both nanoparticle types did not induce acute toxicity to the different organs evaluated, reinforcing the biocompatibility of PTEe nanoparticles synthetized by thiol-ene polymerization.

Recently, research about droplet self-transportation on slippery surfaces has become a hotspot. However, to achieve on/off sliding control during the self-transportation process is still difficult. Herein, we report a magnetic slippery surface, and demonstrate on/off sliding control during the self-transportation of superparamagnetic droplets. The surface is prepared through integrating a substrate that has a gradient magnetic region with a layer of paraffin infused hydrophobic SiO

Overuse of antibiotics has led to the development of multi drug resistant strains. Antibiotic resistance is a major drawback in the biomedical field since medical implants are prone to infection by biofilms of antibiotic resistant strains of bacteria. With increasing prevalence of antibiotic resistant pathogenic bacteria, the search for alternative method is utmost importance. In this regard, magnetic nanoparticles are commonly used as a substitute for antibiotics that can circumvent the problem of biofilms growth on the surface of biomedical implants. Iron oxide nanoparticles (IONPs) have unique magnetic properties that can be exploited in various ways in the biomedical applications. IONPs are engineered employing different methods to induce surface functionalization that include the use of polyethyleneimine and oleic acid. IONPs have a mechanical effect on biofilms when in presence of an external magnet. In this review, a detailed description of surface engineered magnetic nanoparticles as ideal antibacterial agents is provided, accompanied by various methods of literature review. This article is protected by copyright. All rights reserved.

Ferroptosis is a form of cell death associated with iron-dependent lipid peroxidation. We used a chicken embryo model to investigate if ferroptosis was implicated in the molecular mechanism underlying the potential effects of maternal exposure to iron oxide nanoparticles (IONPs) on the developing brain. One hundred and eighty fertilized eggs were randomly divided into six groups (30 eggs/group; 10 eggs/replicate). Groups I and II received maghemite (γ-Fe2 O3 ) NPs (MGMNPs), while groups III and IV received magnetite (Fe3 O4 ) NPs (MGTNPs). Both MGMNP and MGTNP were administrated at the concentrations of 100 and 250 ppm. One group (placebo) received saline, and the other remained untreated (control). The compounds were given by in ovo method (0.3 ml/egg) only once on the first day of the embryonic period. Samples from cerebral tissue were collected on day 20 for histopathological, biochemical and gene expression analyses. Total antioxidant capacity (TAC) and malondialdehyde (MDA) increased; glutathione peroxidase (GPX) expression and activity decreased in IONPs-treated groups. Ferroptotic cells appeared in the cerebral tissue following exposure to the low dose of MGMNP and MGTNP. Oxidative stress and ferroptotic cells were more evident for MGMNP compared to MGTNP. The low dose of MGMNP and MGTNP induced more severe oxidative stress in the cerebral tissue. According to the results, maternal exposure to IONPs is associated with ferroptosis in the brain. This work could encourage future researches to investigate inhibitors of ferroptosis as a protective strategy against iron-induced cell injuries and cell death.

Summary Autoimmune diseases are caused by adaptive immune responses to self‐antigens. The development of antigen‐specific therapies that suppress disease‐related, but not unrelated immune responses in general, is an important goal of biomedical research. We have previously shown that delivery of myelin peptides to liver sinusoidal endothelial cells (LSECs) using LSEC‐targeting nanoparticles provides effective protection from CD4 T‐cell‐driven autoimmune encephalomyelitis. Here, we investigated whether this methodology might also serve antigen‐specific treatment of a CD8 T‐cell‐driven autoimmune disease. As a model for CD8 T‐cell‐mediated autoimmunity, we used OT‐1 T‐cell‐driven cholangitis in K14‐OVAp mice expressing the cognate MHC I‐restricted SIINFEKL peptide in cholangiocytes. To study whether peptide delivery to LSECs could modulate cholangitis, SIINFEKL peptide‐conjugated nanoparticles were administered intravenously one day before transfer of OT‐1 T cells; five days after cell transfer, liver pathology and hepatic infiltrates were analysed. SIINFEKL peptide‐conjugated nanoparticles were rapidly taken up by LSECs in vivo, which effectively cross‐presented the delivered peptide on MHC I molecules. Intriguingly, K14‐OVAp mice receiving SIINFEKL‐loaded nanoparticles manifested significantly reduced liver damage compared with vehicle‐treated K14‐OVAp mice. Mechanistically, treatment with LSEC‐targeting SIINFEKL‐loaded nanoparticles significantly reduced the number of liver‐infiltrating OT‐1 T cells, which up‐regulated expression of the co‐inhibitory receptor PD‐1 and down‐regulated cytotoxic effector function and inflammatory cytokine production. These findings show that tolerogenic LSECs can effectively internalize circulating nanoparticles and cross‐present nanoparticle‐bound peptides on MHC I molecules. Therefore, nanoparticle‐mediated autoantigen peptide delivery to LSECs might serve the antigen‐specific treatment of CD8 T‐cell‐driven autoimmune disease., We show that CD8 T‐cell‐mediated bile duct damage can be prevented by targeting the specific epitope peptides to liver sinusoidal endothelial cells in vivo using nanoparticles. These cells effectively cross‐present the received peptides and induce CD8 T‐cell tolerance.

Although incorporating proteases into sperm medium is considered the most effective procedure to eliminate camel semen viscosity, it drastically affects viability, morpho-functional properties and, hence, fertilization potential of spermatozoa. The present work aimed at evaluating adequacy of employing magnetic nanoparticles-based sperm purification technique for eluting impaired and apoptotic camel spermatozoa from cryopreserved semen doses following protease-based semen liquefaction. Thirty cryopreserved semen doses (50 x 106 sperm/straw) representing the following liquefaction treatments: control (untreated), 0.1 mg/ml papain or 5 U/ml bromelain were used (n = 10 straws per treatment). Immediately after thawing (38°C for 40 s), sperm concentration of each straw within treatment was readjusted to 15 x 106 sperm/mL by dilution in PBS (37°C). Sperm physical and cytological properties were then assessed (non-purified semen). Thereafter, each specimen was subjected to lectin-functionalized DNA-defrag magnetic nanoparticles sperm purification, and the same sperm traits were re-evaluated after undergoing purification (purified semen). Sperm DNA fragmentation level within each group, prior to and after magnetic nano-purification, was also determined by fluorescent imaging. The results showed a dramatic improvement (p < .05) in post-thaw motility (%), viability (%), normal sperm (%), intact acrosome (%) and HOST-reacted (%) spermatozoa in protease-liquefied semen following sperm magnetic nano-purification. Additionally, the highest (p < .05) DNA fragmentation level was recorded in all cryopreserved semen groups prior to purification, whereas the lowest (p < .05) was observed in the protease-treated specimens after magnetic nano-purification. These results indicate that protease-based semen liquefaction prior to cryopreservation in conjunction with magnetic nano-purification post-thawing holds potential for reducing the proportion of damaged and dead spermatozoa, hence improving camel sperm fertilization competence.

Researches have proved that increasing level of prostate-specific antigen (PSA) is an indicator for the progression of prostate cancer. The present study was focused to determine the PSA level by using anti-PSA antibody conjugated iron oxide nanoparticles, as the probe immobilized on the gap-fingered electrode sensing surface. The detection limit and sensitivity were found at the level of 1.9 pg/mL on the linear regression curve (y = 1.6939x - 0.5671; R² = 0.9878). A dose-dependent liner range was found from 1.9 until 60 pg/mL. Further, PSA was spiked in human serum and did not affect the interaction of PSA and its antibody. This method of detection quantifies the level of PSA, which helps to diagnose prostate cancer at its earlier stage.

Unpredictable in vivo therapeutic feedback of hydroxyl radical (•OH) efficiency is the major bottleneck of chemodynamic therapy. Herein, we describe novel Fenton-based nanotheranostics NQ-Cy@Fe&GOD for spatio-temporally reporting intratumor •OH-mediated treatment, which innovatively unites dual-channel near-infrared (NIR) fluorescence and magnetic resonance imaging (MRI) signals. Specifically, MRI signal traces the dose distribution of Fenton-based iron oxide nanoparticles (IONPs) with high-spatial resolution, meanwhile timely fluorescence signal quantifies •OH-mediated therapeutic response with high spatio-temporal resolution. NQ-Cy@Fe&GOD can successfully monitor the intracellular release of IONPs and •OH-induced NQO1 enzyme in living cells and tumor-bearing mice, which makes a breakthrough in conquering the inherent unpredictable obstacles on spatio-temporally reporting chemodynamic therapy, so as to manipulate dose-dependent therapeutic process. This unprecedented strategy can elaborately bridge MRI and fluorescence imaging modality with spatio-temporal resolution, and paves a new pathway for accurately evaluating in situ generation of •OH feedback on the intratumoral catalytic Fenton reaction.

In pursuit of a preventive therapeutic for maternal autoantibody-related (MAR) autism, we assessed the toxicity, biodistribution, and clearance of a MAR specific peptide-functionalized dextran iron oxide nanoparticle system in pregnant murine dams. We previously synthesized ~15 nm citrate-coated dextran iron oxide nanoparticles (DIONPs), surface-modified with polyethylene glycol and MAR peptides to produce systems for nanoparticle-based autoantibody reception and entrapments (SNAREs). First, we investigated their immunogenicity and MAR lactate dehydrogenase B antibody uptake in murine serum in vitro. To assess biodistribution and toxicity, as well as systemic effects, we performed in vivo clinical and post mortem pathological evaluations. We observed minimal production of inflammatory cytokines—interleukin 10 (IL-10) and IL-12 following in vitro exposure of macrophages to SNAREs. We established the maximum tolerated dose of SNAREs to be 150 mg/kg at which deposition of iron was evident in the liver and lungs by histology and magnetic resonance imaging but no concurrent evidence of liver toxicity or lung infarction was detected. Further, SNAREs exhibited slower clearance from the maternal blood in pregnant dams compared to DIONPs based on serum total iron concentration. These findings demonstrated that the SNAREs have a prolonged presence in the blood and are safe for use in pregnant mice as evidenced by no associated organ damage, failure, inflammation, and fetal mortality. Determination of the MTD dose sets the basis for future studies investigating the efficacy of our nanoparticle formulation in a MAR autism mouse model.

The aim of this study was to investigate in vitro magnetic resonance imaging (MRI) of PDAC using ENO1‐targeted superparamagnetic iron oxide nanoparticles and xenograft models. Expression level and location of ENO1 protein in pancreatic cancer cell lines of CFPAC‐1 and MiaPaCa‐2 were detected by Western blotting, flow cytometry and confocal microscopy. Dex‐g‐PCL/SPIO nanoparticles targeting ENO1 were constructed with ENO1 antibody and characterized by MRI. In addition, ENO1‐Dex‐g‐PCL/SPIO nanoparticles were tested to assess their efficacy on the detection of PDAC using in vitro and in vivo MRI. The results showed that ENO1 was expressed in both human PDAC cell lines of CFPAC‐1 and MiaPaCa‐2, demonstrating that the localization of cytoplasm and membrane was dominant. It was confirmed that ENO1 antibody was connected to the SPIO surface in ENO1‐Dex‐g‐PCL/SPIO nanoparticles. The nanoparticles had satisfactory superparamagnetism and significantly enhance the detection of PDAC by in vivo and in vitro MRI. In conclusion, ENO1 can serve as a membrane protein expressed on human PDAC cell lines. ENO1‐targeted SPIO nanoparticles using ENO1 antibody can increase the efficiency of detection of PDAC by in vitro and in vivo MRI.

Superparamagnetic iron oxide nanoparticles (SPIONs) are extensively applied in biomedical fields, such as magnetic resonance imaging and as nanocarriers. However, the biosafety of SPIONs is not completely established, especially their effect on the immune system and inflammatory responses. Toll-like receptor (TLR) signaling is essential for many acute and chronic human inflammatory diseases. Regulation of TLR responses with drugs is helpful for these inflammatory conditions. In this study, we investigated the effects of 10 and 30 nm SPIONs on macrophages in the presence or absence of the TLR4 agonist lipopolysaccharide (LPS). We found that SPIONs inhibited the release of inflammatory cytokines induced by LPS both in murine and human macrophages in a concentration-dependent manner. Meanwhile, SPIONs suppressed inducible nitric oxide synthase expression activated by SPIONs in RAW264.7 macrophages. Additionally, TLR4 mRNA transcription and expression were attenuated with SPIONs treatment, which positively correlated with the release of inflammatory cytokines. In summary, our study demonstrates that SPIONs can suppress inflammatory responses, and the underlying mechanism may be regulated by TLR4 expression. Our present work contributes to clarifying the biosafety of SPIONs and provides a potential approach to alleviate human inflammatory diseases.

During evolution, sponges (Porifera) have honed the genetic toolbox and biosynthetic mechanisms for the fabrication of siliceous skeletal components (spicules). Spicules carry a protein scaffold embedded within biogenic silica (biosilica) and feature an amazing range of optical, structural, and mechanical properties. Thus, it is tempting to explore the low-energy synthetic pathways of spiculogenesis for the fabrication of innovative hybrid materials. In this synthetic biology approach, the uptake of multifunctional nonbiogenic nanoparticles (fluorescent, superparamagnetic) by spicule-forming cells of bioreactor-cultivated sponge primmorphs provides access to spiculogenesis. The ingested nanoparticles were detected within intracellular vesicles resembling silicasomes (silica-rich cellular compartments) and as cytosolic clusters where they lent primmorphs fluorescent/magnetic properties. During spiculogenesis, the nanoparticles initially formed an incomplete layer around juvenile, intracellular spicules. In the mature, extracellular spicules the nanoparticles were densely arranged as a surface layer that rendered the resulting composite fluorescent and magnetic. By branching off the conventional route of solid-state materials synthesis under harsh conditions, a new pathway has been opened to a versatile platform that allows adding functionalities to growing spicules as templates in living cells, using nonbiogenic nanoscale building blocks with multiple functionalities. The magnet-assisted alignment renders this composite with its fluorescent/magnetic properties potentially suitable for application in biooptoelectronics and microelectronics (e.g., microscale on-chip waveguides for applications of optical detection and sensing).

Ultrasmall superparamagnetic iron oxide nanoparticles (USPION) possess reactive surfaces, are metabolized and exhibit unique magnetic properties. These properties are desirable for designing novel theranostic biomedical products; however, toxicity mechanisms of USPION are not completely elucidated. The goal of this study was to investigate cell interactions (uptake and cytotoxicity) of USPION using human coronary artery endothelial cells as a vascular cell model. Polyvinylpirrolidone-coated USPION were characterized: average diameter 17 nm (transmission electron microscopy [TEM]), average hydrodynamic diameter 44 nm (dynamic light scattering) and zeta potential -38.75 mV. Cells were exposed to 0 (control), 25, 50, 100 or 200 μg/mL USPION. Concentration- and time-dependent cytotoxicity were observed after 3-6 hours through 24 hours of exposure using Alamar Blue and Real-Time Cell Electronic Sensing assays. Cell uptake was evaluated by imaging using live-dead confocal microscopy, actin and nuclear fluorescent staining, and TEM. Phase-contrast, confocal microscopy, and TEM imaging showed significant USPION internalization as early as 3 hours after exposure to 25 μg/mL. TEM imaging demonstrated particle internalization in secondary lysosomes with perinuclear localization. Three orthogonal assays were conducted to assess apoptosis. TUNEL staining demonstrated a marked increase in fragmented DNA, a response pathognomonic of apoptosis, after a 4-hour exposure. Cells subjected to agarose gel electrophoresis exhibited degraded DNA 3 hours after exposure. Caspase-3/7 activity increased after a 3-hour exposure. USPION uptake resulted in cytotoxicity involving apoptosis and these results contribute to further mechanistic understanding of the USPION toxicity in vitro in cardiovascular endothelial cells.

Iron oxide nanoparticles are nanomaterials that are used extensively in the biomedical field, but they are associated with adverse effects, including mitochondrial toxicity. Mitochondrial homeostasis is achieved through dynamic stability based on two sets of antagonistic balanced processes: mitochondrial biogenesis and degradation as well as mitochondrial fission and fusion. In this study, we showed that PEG-COOH-coated Fe3 O4 (PEG-Fe3 O4 ) nanoparticles induced mitochondrial instability in dendritic cells (DCs) by impairing mitochondrial dynamics due to promotion of mitochondrial biogenesis through activation of the peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) pathway, inhibiting mitochondrial degradation via decreased autophagy, and facilitating mitochondrial fragmentation involving increased levels of DRP1 and MFN2. The resulting reduced levels of dextran uptake, CD80, CD86 and chemokine receptor 7 (CCR7) suggested that PEG-Fe3 O4 nanoparticles impaired the functionally immature state of DCs. Autophagy inhibitor 3-methyladenine (3-MA) alleviated PEG-Fe3 O4 nanoparticle-induced mitochondrial instability and impairment of the functionally immature state of DCs due to unexpected enhancement of PGC1α/MFN2-mediated coordination of mitochondrial biogenesis and fusion.

Purpose Herein, we evaluate the use of MRI as a tool for assessing iron oxide nanoparticle (IONP) distribution within IONP perfused organs and vascularized composite allografts (VCAs) (i.e., hindlimbs) prepared for cryopreservation. Methods Magnetic resonance imaging was performed on room-temperature organs and VCAs perfused with IONPs and were assessed at 9.4 T. Quantitative T1 mapping and T 2 ∗ -weighted images were acquired using sweep imaging with Fourier transformation and gradient-echo sequences, respectively. Verification of IONP localization was performed through histological assessment and microcomputer tomography. Results Quantitative imaging was achieved for organs and VCAs perfused with up to 642 mMFe (36 mgFe /mL), which is above previous demonstrations of upper limit detection in agarose (35.7mMFe [2 mgFe /mL]). The stability of IONPs in the perfusate had an effect on the quality of distribution and imaging within organs or VCA. Finally, MRI provided more accurate IONP localization than Prussian blue histological staining in this system, wherein IONPs remain primarily in the vasculature. Conclusion Using MRI, we were able to assess the distribution of IONPs throughout organs and VCAs varying in complexity. Additional studies are necessary to better understand this system and validate the calibration between T1 measurements and IONP concentration.

Islet transplantation is a potential treatment option for certain patients with type 1 diabetes; however, it still faces barriers to widespread use, including the lack of tools to monitor islet grafts post-transplantation. This study investigates whether labeling neonatal porcine islets (NPI) with polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles (PVP-SPIO) affects their function, and whether this nanoparticle can be utilized to monitor NPI xenografts with magnetic resonance imaging (MRI) in a mouse model. In vitro, PVP-SPIO-labeled NPI in an agarose gel was visualized clearly by MRI. PVP-SPIO-labeled islets were then transplanted under the kidney capsules of immunodeficient nondiabetic and diabetic mice. All diabetic mice that received transplantation of PVP-SPIO-labeled islets reached normoglycemia. Grafts appeared as hypo-intense areas on MRI and were distinguishable from the surrounding tissues. Following injection of spleen cells from immunocompetent mice, normoglycemic recipient mice became diabetic and islet grafts showed an increase in volume, accompanied by a mixed signal on MRI. Overall, this study demonstrates that PVP-SPIO did not affect the function of NPI that PVP-SPIO-labeled islets were easily seen on MRI, and changes in MRI signals following rejection suggest a potential use of PVP-SPIO-labeled islets to monitor graft viability.

Plasmonic nanoparticles that can be manipulated with magnetic fields are of interest for advanced optical applications, diagnostics, imaging, and therapy. Alignment of gold nanorods yields strong polarization-dependent extinction, and use of magnetic fields is appealing because they act through space and can be quickly switched. In this work, cationic polyethyleneimine-functionalized superparamagnetic Fe

Mimicking the structure of extracellular matrix (ECM) of myocardium is necessary for fabrication of functional cardiac tissue. The superparamagnetic iron oxide nanoparticles (SPIONs, Fe3 O4 ), as new generation of magnetic nanoparticles (NPs), are highly intended in biomedical studies. Here, SPION NPs (1 wt%) were synthesized and incorporated into silk-fibroin (SF) electrospun nanofibers to enhance mechanical properties and topography of the scaffolds. Then, the mouse embryonic cardiac cells (ECCs) were seeded on the scaffolds for in vitro studies. The SPION NPs were studied by scanning electron microscope (SEM), X-ray diffraction (XRD), and transmission electron microscope (TEM). SF nanofibers were characterized after incorporation of SPIONs by SEM, TEM, water contact angle measurement, and tensile test. Furthermore, cytocompatibility of scaffolds was confirmed by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. SEM images showed that ECCs attached to the scaffolds with elongated morphologies. Also, the real-time PCR and immunostaining studies approved upregulation of cardiac functional genes in ECCs seeded on the SF/SPION-casein scaffolds including GATA-4, cardiac troponin T, Nkx 2.5, and alpha-myosin heavy chain, compared with the ones in SF. In conclusion, incorporation of core-shells in SF supports cardiac differentiation, while has no negative impact on ECCs' proliferation and self-renewal capacity.

Because of the insufficiency of hydrogen peroxide, the relatively low rate of Fenton reaction, and the active glutathione (GSH) peroxidase 4 (GPX4) in tumor cells, it is difficult to achieve a desirable efficacy of ferroptosis therapy (FT) for tumors based on nanomaterials. Inspired by the concept of "cyclotron" in physics, in this study, a new concept of cycloacceleration of reactive oxygen species (ROS) generation in tumor cells to realize high-performance FT of tumors is proposed. Typically, a magnetic resonance imaging (MRI) contrast agent of dotted core-shell Fe

E.X. and R.M. contributed equally to this work. Work partially supported by the Ministerio de Ciencia, Innovacion y Universidades (PID2019-106301RB-I00 and PID2019-105195RA-I00), by the Spanish Ministry of Economy and Competitiveness (MAT2017-85617-R, SEV-2016-0686), by the Comunidad de Madrid (RENIM-CM, B2017/BMD-3867, co-financed by the European Structural and Investment Fund; NANOMAGCOST-CM P2018/NMT-4321), by the European COST Actions CA17115 (MyWave) and CA17140 (Nano2Clinic), by the Spanish Scientific Network HiperNano (RED2018-102626-T) and by the European Commission Horizon 2020 project NanoTBTech (Grant Number: 801305). D.G.-C. acknowledges CAM for funding PEJ-2018-AI/IND-11245. A.B. acknowledges funding from Comunidad de Madrid through TALENTO grant ref. 2019-T1/IND-14014. E.X. is grateful for a Juan de la Cierva Formacion scholarship (FJC2018-036734-I). R.M. acknowledges the support of the European Commission through the European Union's Horizon 2020 research and innovation program under the Marie Skodowska-Curie Grant agreement N 797945 (LANTERNS). A. E. acknowledges the support from Comunidad de Madrid (Talento project 2018-T1/IND-1005) and from AECC (Ideas Semilla 2019 project). P.R.S. is grateful for a Juan de la Cierva Incorporacion scholarship (IJC2019-041915-I). Procedures involving animal experiments were approved by the regional authority for animal experimentation of the Comunidad de Madrid and were conducted in agreement with the Universidad Autonoma de Madrid Ethics Committee, in compliance with the European Union directives 63/2010UE and Spanish regulation RD 53/2013., Deliberate and local increase of the temperature within solid tumors represents an effective therapeutic approach. Thermal therapies embrace this concept leveraging the capability of some species to convert the absorbed energy into heat. To that end, magnetic hyperthermia (MHT) uses magnetic nanoparticles (MNPs) that can effectively dissipate the energy absorbed under alternating magnetic fields. However, MNPs fail to provide real-time thermal feedback with the risk of unwanted overheating and impeding on-the-fly adjustment of the therapeutic parameters. Localization of MNPs within a tissue in an accurate, rapid, and cost-effective way represents another challenge for increasing the efficacy of MHT. In this work, MNPs are combined with state-of-the-art infrared luminescent nanothermometers (LNTh; Ag2S nanoparticles) in a nanocapsule that simultaneously overcomes these limitations. The novel optomagnetic nanocapsule acts as multimodal contrast agents for different imaging techniques (magnetic resonance, photoacoustic and near-infrared fluorescence imaging, optical and X-ray computed tomography). Most crucially, these nanocapsules provide accurate (0.2 degrees C resolution) and real-time subcutaneous thermal feedback during in vivo MHT, also enabling the attainment of thermal maps of the area of interest. These findings are a milestone on the road toward controlled magnetothermal therapies with minimal side effects., Ministerio de Ciencia, Innovacion y Universidades PID2019-106301RB-I00 PID2019-105195RA-I00, Spanish Ministry of Economy and Competitiveness MAT2017-85617-R SEV-2016-0686, Comunidad de Madrid (RENIM-CM - European Structural and Investment Fund) B2017/BMD-3867 NANOMAGCOST-CM P2018/NMT-4321, Spanish Scientific Network HiperNano RED2018-102626-T, European Commission Horizon 2020 project NanoTBTech 801305, CAM PEJ-2018-AI/IND-11245, Comunidad de Madrid 2019-T1/IND-14014, Juan de la Cierva Formacion scholarship FJC2018-036734-I, European Commission through the European Union's Horizon 2020 research and innovation program under the Marie Skodowska-Curie Grant 797945, Juan de la Cierva Incorporacion scholarship IJC2019-041915-I, Comunidad de Madrid 2018-T1/IND-1005, AECC (Ideas Semilla 2019 project), European COST Action (MyWave) CA17115, European COST Action (Nano2Clinic) CA17140

Iron oxide nanoparticles (IONPs) possess many utilizable physical and chemical properties and have an acceptable level of biocompatibility. Therefore, they are extensively used in different medical applications. Hence, the challenge is to modify the surfaces of prepared iron oxide nanoformulations with a biocompatible coat to enhance their biosafety. In this study, different formulations of IONPs with different capping agents (citrate [Cit-IONPs], curcumin [Cur-IONPs], and chitosan [CS-IONPs]) were prepared and characterized using various physicochemical techniques. The biodistribution of iron and the histopathology of affected tissues were assessed after Cit-IONPs, Cur-IONPs, CS-IONPs, and commercial ferrous sulfate were orally administered to adult female Wistar rats for 10 consecutive days at a dose of 4 mg/kg of body weight/day. The results were compared with a control group injected orally with saline. The iron content in the kidneys, liver, and spleen was measured by atomic absorption spectroscopy. Histopathological alterations were also examined. The biodistribution results demonstrate that iron accumulated mainly in the liver tissue, whereas the lowest liver accumulation was observed after the administration of Cit-IONPs or CS-IONPs, respectively. In contrast, the administration of CS-IONPs displayed the highest spleen iron accumulation. The ferrous sulfate (FeSO4 )-treated group showed the highest kidney iron accumulation as compared with the other groups. The histopathological examination revealed that signs of toxicity were predominant for groups treated with Cit-IONPs or commercial FeSO4 . However, Cur-IONPs and CS-IONPs showed mild toxicity when administered at the same doses. The results obtained in the present study will provide insights into the expected in vivo effects after administration of each nanoformulation.

Prostate cancer is among the leading causes of death worldwide because its metastatic form is a deadly disease. Therefore, the development of new chemotherapeutics is of immense importance. Nanoparticle technology seems to provide diverse options in this regard. Therefore, poly(N-isopropylacrylamide) (PNIPAM) coated superparamagnetic iron oxide nanoparticles (SPION) loaded with etoposide were prepared in small sizes (57 nm) and with 3.5% drug content to improve the efficiency of etoposide in prostate cancer therapy. Sustained release of the drug was achieved, which found to be sensitive to low pH and high temperature. The anti-growth activity of SPION-PNIPAM-Etoposide formulation against metastatic prostate cancer cells (PC-3, LNCaP) were investigated by SRB assay, then confirmed by ATP assay. Mode of cell death was evaluated by using flow cytometry analyses. A significant improvement of nanoformulated drug was observed at 5-10 μg/ml doses of the drug in both cell lines. More importantly, this formulation enhanced the cytotoxic effect of etoposide on PC-3 cells, which is considered more resistant to etoposide than LNCaP, and reduced the IC 50 by 55% reaching to 4.5 μg drug/ml, which is a very significant improvement in the literature. It was clearly shown that nanoformulated drug provided about 3 fold increases in caspase-dependent early apoptotic cells in PC-3 cells. The novel formulation seems to successfully cause cell death of especially PC-3 metastatic prostate cancer cells. It should therefore be taken into consideration for further animal studies as a novel potent anticancer agent. WOS:000577750400001 32918383 Q3

Today, it has been proven that the nanoparticles such as superparamagnetic iron oxide nanoparticles (SPIONs) have widespread use in biomedical applications, for instance, in magnetic resonance imaging and targeted delivery of drugs. Despite many studies on SPIONs in diagnosing some diseases like cancer, it has not been investigated on the oral tongue squamous cell carcinoma (OTSCC) detection by the NPs. Hence, the present study has been designed to assess the in vitro cytotoxicity of SPIONs on the isolated mitochondria of OTSCC by mitochondrial tests. Isolated mitochondria were removed from the separated cancer and control tissues from the squamous cells of tango in male Wistar rats (6 or 8 weeks) and exposed to the different concentrations of SPIONs (30, 60, and 120 nM). A rise in the production of reactive oxygen species is one of the significant mechanisms of this study, followed by a collapse of mitochondrial membrane potential, the escape of mitochondrial cytochrome c, and mitochondrial swelling in the exposed isolated mitochondria of OTSCC with SPIONs. Furthermore, our results indicated that the exposure to the SPIONs reduced the activity of succinate dehydrogenase in complex II of the mitochondria obtained from cancerous oral tongue squamous. So the SPIONs can induce selective cytotoxicity on the OTSCC mitochondria without significant effects on the control mitochondria. Based on the results and further studies about in vivo experiments in this regard, it is concluded the SPIONs may be a hopeful therapeutic candidate for the treatment of OTSCC.

Rationale Sedatives, which are prone to cause residues in animals, have been abused in modern animal husbandry. Long-term consumption of contaminated meat products would be unfavorable to the human nervous system. Taking into account public health and food safety, it was essential to develop an effective method for the enrichment and detection of sedatives in meat. Methods Fe3 O4 @TbBd@ZIF-8 composites were synthesized by using Fe3 O4 nanoparticles as a magnetic core and 1,3,5-triformylbenzene (Tb) and benzidine (Bd) as two building blocks to form Fe3 O4 @TbBd. Furthermore, the zeolitic imidazolate framework-8 (ZIF-8) was modified on the surface of the Fe3 O4 @TbBd. In addition, Fe3 O4 @TbBd@ZIF-8 was used as a magnetic solid-phase extraction (MSPE) adsorbent of typical animal sedatives in pork samples. Mass spectrometry analysis was conducted by electrospray ionization triple-quadrupole mass spectrometry in positive-ion multiple reaction monitoring mode. Results By combining the optimized MSPE approach with high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS), an accurate and sensitive method for the determination of sedatives was developed. The method exhibited good linearity in the range of 0.03-70 μg/kg with the correlation coefficient (R2 ) ranging from 0.9982 to 0.9999, high sensitivity with limits of detection (LODs) ranging from 0.04 to 0.2 μg/kg, and high precision with relative standard deviation (RSD) less than 5.5%. The adsorption behaviors of Fe3 O4 @TbBd@ZIF-8 towards sedatives were more suitably described by a pseudo-second-order kinetic and Freundlich isotherm model. Conclusions The proposed MSPE-HPLC/MS/MS method was successfully applied to the determination of sedatives in real samples and showed excellent applicability. Several sedatives were detected in the selected meat samples. The developed method was shown to be facile, sensitive and accurate for sedative detection and also showed great prospects for determination of sedatives from other complex samples.

Ubiquitous pollution by microplastics is causing significant deleterious effects on marine life and human health through the food chain and has become a big challenge for the global ecosystem. It is of great urgency to find a cost-efficient and biocompatible material to remove microplastics from the environment. Mimicking basic characteristics of the adhesive chemistry practiced by marine mussels, adhesive polydopamine (PDA)@Fe

Gene delivery to stem cells is a critical issue of stem cells-based therapies, still facing ongoing challenges regarding efficiency and safety. Recent advances in the controlled synthesis of biocompatible magnetic iron oxide nanoparticles (IONPs) have provided a powerful nanotool for assisting gene delivery to stem cells. However, this field is still at an early stage, with well-designed and scalable IONPs synthesis highly desired. Furthermore, the potential risks or bioeffects of IONPs on stem cells are not completely figured out. Therefore, in this review, the updated researches focused on the gene delivery to stem cells using various designed IONPs are highlighted. Additionally, the impacts of the physicochemical properties of IONPs, as well as the magnetofection systems on the gene delivery performance and biocompatibility are summarized. Finally, challenges attributed to the potential impacts of IONPs on the biologic behaviors of stem cells and the large-scale productions of uniform IONPs are emphasized. The principles and challenges summarized in this review provide a general guidance for the rational design of IONPs-assisted gene delivery to stem cells.