Development and Characterization of Curcumin-Silver Nanoparticles as a Promising Formulation to Test on Human Pterygium-Derived Keratinocytes.

Pterygium is a progressive disease of the human eye arising from sub-conjunctival tissue and extending onto the cornea. Due to its invasive growth, pterygium can reach the pupil compromising visual function. Currently available medical treatments have limited success in suppressing efficiently the disease. Previous studies have demonstrated that curcumin, polyphenol isolated from the rhizome of Curcuma longa, induces apoptosis of human pterygium fibroblasts in a dose- and time-dependent manner showing promising activity in the treatment of this ophthalmic disease. However, this molecule is not very soluble in water in either neutral or acidic pH and is only slightly more soluble in alkaline conditions, while its dissolving in organic solvents drastically reduces its potential use for biomedical applications. A nanoformulation of curcumin stabilized silver nanoparticles (Cur-AgNPs) seems an effective strategy to increase the bioavailability of curcumin without inducing toxic effects. In fact, silver nitrates have been used safely for the treatment of many ophthalmic conditions and diseases for a long time and the concentration of AgNPs in this formulation is quite low. The synthesis of this new compound was achieved through a modified Bettini's method adapted to improve the quality of the product intended for human use. Indeed, the pH of the reaction was changed to 9, the temperature of the reaction was increased from 90 °C to 100 °C and after the synthesis the Cur-AgNPs were dispersed in Borax buffer using a dialysis step to improve the biocompatibility of the formulation. This new compound will be able to deliver both components (curcumin and silver) at the same time to the affected tissue, representing an alternative and a more sophisticated strategy for the treatment of human pterygium. Further in vitro and in vivo assays will be required to validate this formulation.

Current advances in the detection of COVID-19 and evaluation of the humoral response.

The new outbreak caused by coronavirus SARS-CoV-2 started at the end of 2019 and was declared a pandemic in March 2020. Since then, several diagnostic approaches have been re-adapted, and also improved from the previous detections of SARS and MERS coronavirus. The best strategy to handle this situation seems to rely on a triad of detection methods: (i) highly sensitive and specific techniques as the gold standard method, (ii) easier and faster point of care tests accessible for large population screening, and (iii) serology assays to complement the direct detection and to use for surveillance. In this study, we assessed the techniques and tests described in the literature, their advantages and disadvantages, and the interpretation of the results. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) is undoubtedly the gold standard technique utilized not only for diagnostics, but also as a standard for comparison and validation of newer approaches. Other nucleic acid amplification methods have been shown to be adequate as point of care (POC) diagnostic tests with similar performance as RT-qPCR. The analysis of seroconversion with immunotests shows the complexity of the immune response to COVID-19. The detection of anti-SARS-CoV-2 antibodies can also help to detect previously infected asymptomatic individuals with negative RT-qPCR tests. Nevertheless, more controlled serology cohort studies should be performed as soon as possible to understand the immune response to SARS-CoV-2.

Bacterial risk factors for treatment failure and relapse among patients with isoniazid resistant tuberculosis.

BACKGROUND: Drug resistant tuberculosis (TB) is increasing in prevalence worldwide. Treatment failure and relapse is known to be high for patients with isoniazid resistant TB treated with standard first line regimens. However, risk factors for unfavourable outcomes and the optimal treatment regimen for isoniazid resistant TB are unknown. This cohort study was conducted when Vietnam used the eight month first line treatment regimen and examined risk factors for failure/relapse among patients with isoniazid resistant TB. METHODS: Between December 2008 and June 2011 2090 consecutive HIV-negative adults (≥18 years of age) with new smear positive pulmonary TB presenting at participating district TB units in Ho Chi Minh City were recruited. Participants with isoniazid resistant TB identified by Microscopic Observation Drug Susceptibility (MODS) had extended follow-up for 2 years with mycobacterial culture to test for relapse. MGIT drug susceptibility testing confirmed 239 participants with isoniazid resistant, rifampicin susceptible TB. Bacterial and demographic factors were analysed for association with treatment failure and relapse. RESULTS: Using only routine programmatic sputum smear microscopy for assessment, (months 2, 5 and 8) 30/239 (12.6%) had an unfavourable outcome by WHO criteria. Thirty-nine patients were additionally detected with unfavourable outcomes during 2 year follow up, giving a total of 69/239 (28.9%) of isoniazid (INH) resistant cases with unfavourable outcome by 2 years of follow-up. Beijing lineage was the only factor significantly associated with unfavourable outcome among INH-resistant TB cases during 2 years of follow-up. (adjusted OR = 3.16 [1.54-6.47], P = 0.002). CONCLUSION: One third of isoniazid resistant TB cases suffered failure/relapse within 2 years under the old eight month regimen. Over half of these cases were not identified by standard WHO recommended treatment monitoring. Intensified research on early identification and optimal regimens for isoniazid resistant TB is needed. Infection with Beijing genotype of TB is a significant risk factor for bacterial persistence on treatment resulting in failure/relapse within 2 years. The underlying mechanism of increased tolerance for standard drug regimens in Beijing genotype strains remains unknown.

A new insight into the thermodynamical criterion for the preparation of semiconductor and metal nanocrystals using a polymerized complexing method.

This work reports the intrinsic thermodynamical criterion for the preparation of metal and semiconductor nanocrystals using a polymerized complexing method. The basic principle of this method is the formation of a polymerized complexing structure between mono-, binary-, or ternary-metallic ions and bonding agents in aqueous or ethylene glycol solutions by evaporation of the solvents. Heat treatment of the complexing structure under N2 atmosphere produces H2 and CH4 gases, which can reduce the oxide crystalline nuclei to semiconductor and metallic nanocrystals. Experimental results show that Te, CdTe, Ag2Te, CuTe, NiTe1.5, CoTe1.5, Bi2Te3, Sb2Te3, Bi-Sb, In2Te3, Ni2.9SnTe2, CuGaTe2, and CuInS2 semiconductors and Bi, Sb, Ag, Cu, and Ni metallic nanocrystals can be prepared by this method. Transmission electron microscopy observations show that the obtained Bi, Ag2Te, Bi2Te3, Sb2Te3, CdTe, and NiTe1.5 nanocrystals have grain sizes in the nanometer range. The types of metallic and semiconductor phase that can be obtained by this method are explained by the thermodynamical criterion based on calculations of the Gibbs free energy and electrode potential. It is proposed that the crystalline phase of the final product is controlled by the change of the Gibbs free energies of the reactions of the metal oxide with reducing gases and the metal oxide redox electrode potentials, not the metal redox standard electrode potentials and electronegativities of the elements. Furthermore, a prediction is presented for the preparation of other kinds of binary and ternary compound based on the thermodynamical criterion. Our results provide new insight into facile and green preparation of semiconductor and metal nanocrystals.

Magnetic iron oxide nanogels for combined hyperthermia and drug delivery for cancer treatment.

Hyperthermia and chemotherapy represent potential modalities for cancer treatments. However, hyperthermia can be invasive, while chemotherapy drugs often have severe side effects. Recent clinical investigations have underscored the potential synergistic efficacy of combining hyperthermia with chemotherapy, leading to enhanced cancer cell killing. In this context, magnetic iron oxide nanogels have emerged as promising candidates as they can integrate superparamagnetic iron oxide nanoparticles (IONPs), providing the requisite magnetism for magnetic hyperthermia, with the nanogel scaffold facilitating smart drug delivery. This review provides an overview of the synthetic methodologies employed in fabricating magnetic nanogels. Key properties and designs of these nanogels are discussed and challenges for their translation to the clinic and the market are summarised.

A Genetic Algorithm for Universal Optimization of Ultrasensitive Surface Plasmon Resonance Sensors with 2D Materials.

We present a general optimization technique for surface plasmon resonance, (SPR) yielding a range of ultrasensitive SPR sensors from a materials database with an enhancement of ∼100%. Applying the algorithm, we propose and demonstrate a novel dual-mode SPR structure coupling SPP and a waveguide mode within GeO2 featuring an anticrossing behavior and an unprecedented sensitivity of 1364 deg/RIU. An SPR sensor operating at wavelengths of 633 nm having a bimetal Al/Ag structure sandwiched between hBN can achieve a sensitivity of 578 deg/RIU. For a wavelength of 785 nm, we optimized a sensor as a Ag layer sandwiched between hBN/MoS2/hBN heterostructures achieving a sensitivity of 676 deg/RIU. Our work provides a guideline and general technique for the design and optimization of high sensitivity SPR sensors for various sensing applications in the future.

Zn doped iron oxide nanoparticles with high magnetization and photothermal efficiency for cancer treatment.

Magnetic nanoparticles (NPs) are powerful agents to induce hyperthermia in tumours upon the application of an alternating magnetic field or an infrared laser. Dopants have been investigated to alter different properties of materials. Herein, the effect of zinc doping into iron oxide NPs on their magnetic properties and structural characteristics has been investigated in-depth. A high temperature reaction with autogenous pressure was used to prepare iron oxide and zinc ferrite NPs of same size and morphology for direct comparison. Pressure was key in obtaining high quality nanocrystals with reduced lattice strain (27% less) and enhanced magnetic properties. Zn0.4Fe2.6O4 NPs with small size of 10.2 ± 2.5 nm and very high saturation magnetisation of 142 ± 9 emu gFe+Zn-1 were obtained. Aqueous dispersion of the NPs showed long term magnetic (up to 24 months) and colloidal stability (at least 6 d) at physiologically mimicking conditions. The samples had been kept in the fridge and had been stable for four years. The biocompatibility of Zn0.4Fe2.6O4 NPs was next evaluated by metabolic activity, membrane integrity and clonogenic assays, which show an equivalence to that of iron oxide NPs. Zinc doping decreased the bandgap of the material by 22% making it a more efficient photothermal agent than iron oxide-based ones. Semiconductor photo-hyperthermia was shown to outperform magneto-hyperthermia in cancer cells, reaching the same temperature 17 times faster whilst using 20 times less material (20 mgFe+Zn ml-1vs. 1 mgFe+Zn ml-1). Magnetothermal conversion was minimally hindered in the cellular confinement whilst photothermal efficiency remained unchanged. Photothermia treatment alone achieved 100% cell death after 10 min of treatment compared to only 30% cell death achieved with magnetothermia at clinically relevant settings for each at their best performing concentration. Altogether, these results suggest that the biocompatible and superparamagnetic zinc ferrite NPs could be a next biomaterial of choice for photo-hyperthermia, which could outperform current iron oxide NPs for magnetic hyperthermia.

Development of a thermochromic lateral flow assay to improve sensitivity for dengue virus serotype 2 NS1 detection.

Dengue disease is a viral infection that has been widespread in tropical regions, such as Southeast Asia, South Asia and South America. A worldwide effort has been made over a few decades to halt the spread of the disease and reduce fatalities. Lateral flow assay (LFA), a paper-based technology, is used for dengue virus detection and identification because of its simplicity, low cost and fast response. However, the sensitivity of LFA is relatively low and is usually insufficient to meet the minimum requirement for early detection. In this study, we developed a colorimetric thermal sensing LFA format for the detection of dengue virus NS1 using recombinant dengue virus serotype 2 NS1 protein (DENV2-NS1) as a model antigen. Plasmonic gold nanoparticles, including gold nanospheres (AuNSPs) and gold nanorods (AuNRs), and magnetic nanoparticles (MNPs), namely iron oxide nanoparticles (IONPs) and zinc ferrite nanoparticles (ZFNPs), were studied for their thermal properties for sensing assays. AuNSPs with 12 nm diameter were chosen due to their great photothermal effect against light-emitting diodes (LEDs). In the thermal sensing assay, a thermochromic sheet is used as a temperature sensor transforming heat into a visible colour. In the typical LFA, the test line is visible at 6.25 ng mL-1 while our thermal sensing LFA offers a visual signal that can be observed at as low as 1.56 ng mL-1. The colorimetric thermal sensing LFA is capable of reducing the limit of detection (LOD) of DENV2-NS1 by 4 times compared to the typical visual readout. The colorimetric thermal sensing LFA can enhance the sensitivity of detection and deliver visuality to the user to translate without the need for an infrared (IR) camera. It has the potential to expand the utilities of LFA and satisfy early diagnostic applications.

Greatly Enhanced Resonant Exciton-Trion Conversion in Electrically Modulated Atomically Thin WS2 at Room Temperature.

Excitonic resonance in atomically thin semiconductors offers a favorite platform to study 2D nanophotonics in both classical and quantum regimes and promises potentials for highly tunable and ultra-compact optical devices. The understanding of charge density dependent exciton-trion conversion is the key for revealing the underlaying physics of optical tunability. Nevertheless, the insufficient and inefficient light-matter interactions hinder the observation of trionic phenomenon and the development of excitonic devices for dynamic power-efficient electro-optical applications. Here, by engaging an optical cavity with atomically thin transition metal dichalcogenides (TMDCs), greatly enhanced exciton-trion conversion is demonstrated at room temperature (RT) and achieve electrical modulation of reflectivity of ≈40% at exciton and 7% at trion state, which correspondingly enables a broadband large phase tuning in monolayer tungsten disulfide. Besides the absorptive conversion, ≈100% photoluminescence conversion from excitons to trions is observed at RT, illustrating a clear physical mechanism of an efficient exciton-trion conversion for extraordinary optical performance. The results indicate that both excitons and trions can play significant roles in electrical modulation of the optical parameters of TMDCs at RT. The work shows the real possibility for realizing electrical tunable and multi-functional ultra-thin optical devices using 2D materials.

Magnetic particle imaging: tracer development and the biomedical applications of a radiation-free, sensitive, and quantitative imaging modality.

Magnetic particle imaging (MPI) is an emerging tracer-based modality that enables real-time three-dimensional imaging of the non-linear magnetisation produced by superparamagnetic iron oxide nanoparticles (SPIONs), in the presence of an external oscillating magnetic field. As a technique, it produces highly sensitive radiation-free tomographic images with absolute quantitation. Coupled with a high contrast, as well as zero signal attenuation at-depth, there are essentially no limitations to where that can be imaged within the body. These characteristics enable various biomedical applications of clinical interest. In the opening sections of this review, the principles of image generation are introduced, along with a detailed comparison of the fundamental properties of this technique with other common imaging modalities. The main feature is a presentation on the up-to-date literature for the development of SPIONs tailored for improved imaging performance, and developments in the current and promising biomedical applications of this emerging technique, with a specific focus on theranostics, cell tracking and perfusion imaging. Finally, we will discuss recent progress in the clinical translation of MPI. As signal detection in MPI is almost entirely dependent on the properties of the SPION employed, this work emphasises the importance of tailoring the synthetic process to produce SPIONs demonstrating specific properties and how this impacts imaging in particular applications and MPI's overall performance.

N-Doped Graphene Quantum Dots/Titanium Dioxide Nanocomposites: A Study of ROS-Forming Mechanisms, Cytotoxicity and Photodynamic Therapy.

Titanium dioxide nanoparticles (TiO2 NPs) have been proven to be potential candidates in cancer therapy, particularly photodynamic therapy (PDT). However, the application of TiO2 NPs is limited due to the fast recombination rate of the electron (e-)/hole (h+) pairs attributed to their broader bandgap energy. Thus, surface modification has been explored to shift the absorption edge to a longer wavelength with lower e-/h+ recombination rates, thereby allowing penetration into deep-seated tumors. In this study, TiO2 NPs and N-doped graphene quantum dots (QDs)/titanium dioxide nanocomposites (N-GQDs/TiO2 NCs) were synthesized via microwave-assisted synthesis and the two-pot hydrothermal method, respectively. The synthesized anatase TiO2 NPs were self-doped TiO2 (Ti3+ ions), have a small crystallite size (12.2 nm) and low bandgap energy (2.93 eV). As for the N-GQDs/TiO2 NCs, the shift to a bandgap energy of 1.53 eV was prominent as the titanium (IV) tetraisopropoxide (TTIP) loading increased, while maintaining the anatase tetragonal crystal structure with a crystallite size of 11.2 nm. Besides, the cytotoxicity assay showed that the safe concentrations of the nanomaterials were from 0.01 to 0.5 mg mL-1. Upon the photo-activation of N-GQDs/TiO2 NCs with near-infrared (NIR) light, the nanocomposites generated reactive oxygen species (ROS), mainly singlet oxygen (1O2), which caused more significant cell death in MDA-MB-231 (an epithelial, human breast cancer cells) than in HS27 (human foreskin fibroblast). An increase in the N-GQDs/TiO2 NCs concentrations elevates ROS levels, which triggered mitochondria-associated apoptotic cell death in MDA-MB-231 cells. As such, titanium dioxide-based nanocomposite upon photoactivation has a good potential as a photosensitizer in PDT for breast cancer treatment.

A versatile non-fouling multi-step flow reactor platform: demonstration for partial oxidation synthesis of iron oxide nanoparticles.

In the last decade flow reactors for material synthesis were firmly established, demonstrating advantageous operating conditions, reproducible and scalable production via continuous operation, as well as high-throughput screening of synthetic conditions. Reactor fouling, however, often restricts flow chemistry and the common fouling prevention via segmented flow comes at the cost of inflexibility. Often, the difficulty of feeding reagents into liquid segments (droplets or slugs) constrains flow syntheses using segmented flow to simple synthetic protocols with a single reagent addition step prior or during segmentation. Hence, the translation of fouling prone syntheses requiring multiple reagent addition steps into flow remains challenging. This work presents a modular flow reactor platform overcoming this bottleneck by fully exploiting the potential of three-phase (gas-liquid-liquid) segmented flow to supply reagents after segmentation, hence facilitating fouling free multi-step flow syntheses. The reactor design and materials selection address the operation challenges inherent to gas-liquid-liquid flow and reagent addition into segments allowing for a wide range of flow rates, flow ratios, temperatures, and use of continuous phases (no perfluorinated solvents needed). This "Lego®-like" reactor platform comprises elements for three-phase segmentation and sequential reagent addition into fluid segments, as well as temperature-controlled residence time modules that offer the flexibility required to translate even complex nanomaterial synthesis protocols to flow. To demonstrate the platform's versatility, we chose a fouling prone multi-step synthesis, i.e., a water-based partial oxidation synthesis of iron oxide nanoparticles. This synthesis required I) the precipitation of ferrous hydroxides, II) the addition of an oxidation agent, III) a temperature treatment to initiate magnetite/maghemite formation, and IV) the addition of citric acid to increase the colloidal stability. The platform facilitated the synthesis of colloidally stable magnetic nanoparticles reproducibly at well-controlled synthetic conditions and prevented fouling using heptane as continuous phase. The biocompatible particles showed excellent heating abilities in alternating magnetic fields (ILP values >3 nH m2 kgFe-1), hence, their potential for magnetic hyperthermia cancer treatment. The platform allowed for long term operation, as well as screening of synthetic conditions to tune particle properties. This was demonstrated via the addition of tetraethylenepentamine, confirming its potential to control particle morphology. Such a versatile reactor platform makes it possible to translate even complex syntheses into flow, opening up new opportunities for material synthesis.

Penicillium digitatum as a Model Fungus for Detecting Antifungal Activity of Botanicals: An Evaluation on Vietnamese Medicinal Plant Extracts.

Medicinal plants play important roles in traditional medicine, and numerous compounds among them have been recognized for their antimicrobial activity. However, little is known about the potential of Vietnamese medicinal plants for antifungal activity. In this study, we examined the antagonistic activity of twelve medicinal plant species collected in Northern Vietnam against Penicillium digitatum, Aspergillus flavus, Aspergillus fumigatus, and Candida albicans. The results showed that the antifungal activities of the crude extracts from Mahonia bealei, Ficus semicordata, and Gnetum montanum were clearly detected with the citrus postharvest pathogen P. digitatum. These extracts could fully inhibit the growth of P. digitatum on the agar medium, and on the infected citrus fruits at concentrations of 300-1000 µg/mL. Meanwhile, the other tested fungi were less sensitive to the antagonistic activity of the plant extracts. In particular, we found that the ethanolic extract of M. bealei displayed a broad-spectrum antifungal activity against all four pathogenic fungi. Analysis of this crude extract by enrichment coupled with high-performance liquid chromatography revealed that berberine and palmatine are major metabolites. Additional inspections indicated berberine as the key compound responsible for the antifungal activity of the M. bealei ethanolic extract. Our study provides a better understanding of the potential of Vietnamese medicinal plant resources for combating fungal pathogens. This work also highlights that the citrus pathogen P. digitatum can be employed as a model fungus for screening the antifungal activity of botanicals.

Environmental STEM Study of the Oxidation Mechanism for Iron and Iron Carbide Nanoparticles.

The oxidation of solution-synthesized iron (Fe) and iron carbide (Fe2C) nanoparticles was studied in an environmental scanning transmission electron microscope (ESTEM) at elevated temperatures under oxygen gas. The nanoparticles studied had a native oxide shell present, that formed after synthesis, an ~3 nm iron oxide (FexOy) shell for the Fe nanoparticles and ~2 nm for the Fe2C nanoparticles, with small void areas seen in several places between the core and shell for the Fe and an ~0.8 nm space between the core and shell for the Fe2C. The iron nanoparticles oxidized asymmetrically, with voids on the borders between the Fe core and FexOy shell increasing in size until the void coalesced, and finally the Fe core disappeared. In comparison, the oxidation of the Fe2C progressed symmetrically, with the core shrinking in the center and the outer oxide shell growing until the iron carbide had fully disappeared. Small bridges of iron oxide formed during oxidation, indicating that the Fe transitioned to the oxide shell surface across the channels, while leaving the carbon behind in the hollow core. The carbon in the carbide is hypothesized to suppress the formation of larger crystallites of iron oxide during oxidation, and alter the diffusion rates of the Fe and O during the reaction, which explains the lower sensitivity to oxidation of the Fe2C nanoparticles.

DMSA-coated cubic iron oxide nanoparticles as potential therapeutic agents.

Aim: Superparamagnetic cubic iron oxide nanoparticles (IONPs) were synthesized and functionalized with meso-2,3-dimercaptosuccinic acid (DMSA) as a potential agent for cancer treatment. Methods: Monodisperse cubic IONPs with a high value of saturation magnetization were synthesized by thermal decomposition method and functionalized with DMSA via ligand exchange reaction, and their cytotoxic effects on HeLa cells were investigated. Results: DMSA functionalized cubic IONPs with an edge length of 24.5 ± 1.9 nm had a specific absorption rate value of 197.4 W/gFe (15.95 kA/m and 488 kHz) and showed slight cytotoxicity on HeLa cells when incubated with 3.3 × 1010, 6.6 × 1010 and 9.9 × 1010 NP/mL for 24, 48 and 72 h. Conclusion: To the best of our knowledge, this is the first study to investigate both the cytotoxic effects of DMSA-coated cubic IONPs on HeLa cells and hyperthermia performance of these nanoparticles.

The Role of Anisotropy in Distinguishing Domination of Néel or Brownian Relaxation Contribution to Magnetic Inductive Heating: Orientations for Biomedical Applications.

Magnetic inductive heating (MIH) has been a topic of great interest because of its potential applications, especially in biomedicine. In this paper, the parameters characteristic for magnetic inductive heating power including maximum specific loss power (SLPmax), optimal nanoparticle diameter (Dc) and its width (ΔDc) are considered as being dependent on magnetic nanoparticle anisotropy (K). The calculated results suggest 3 different Néel-domination (N), overlapped Néel/Brownian (NB), and Brownian-domination (B) regions. The transition from NB- to B-region changes abruptly around critical anisotropy Kc. For magnetic nanoparticles with low K (K < Kc), the feature of SLP peaks is determined by a high value of Dc and small ΔDc while those of the high K (K > Kc) are opposite. The decreases of the SLPmax when increasing polydispersity and viscosity are characterized by different rates of d(SLPmax)/dσ and d(SLPmax)/dη depending on each domination region. The critical anisotropy Kc varies with the frequency of an alternating magnetic field. A possibility to improve heating power via increasing anisotropy is analyzed and deduced for Fe3O4 magnetic nanoparticles. For MIH application, the monodispersity requirement for magnetic nanoparticles in the B-region is less stringent, while materials in the N- and/or NB-regions are much more favorable in high viscous media. Experimental results on viscosity dependence of SLP for CoFe2O4 and MnFe2O4 ferrofluids are in good agreement with the calculations. These results indicated that magnetic nanoparticles in the N- and/or NB-regions are in general better for application in elevated viscosity media.

Stable Iron Oxide Nanoflowers with Exceptional Magnetic Heating Efficiency: Simple and Fast Polyol Synthesis.

Magnetically induced hyperthermia has reached a milestone in medical nanoscience and in phase III clinical trials for cancer treatment. As it relies on the heat generated by magnetic nanoparticles (NPs) when exposed to an external alternating magnetic field, the heating ability of these NPs is of paramount importance, so is their synthesis. We present a simple and fast method to produce iron oxide nanostructures with excellent heating ability that are colloidally stable in water. A polyol process yielded biocompatible single core nanoparticles and nanoflowers. The effect of parameters such as the precursor concentration, polyol molecular weight as well as reaction time was studied, aiming to produce NPs with the highest possible heating rates. Polyacrylic acid facilitated the formation of excellent nanoheating agents iron oxide nanoflowers (IONFs) within 30 min. The progressive increase of the size of the NFs through applying a seeded growth approach resulted in outstanding enhancement of their heating efficiency with intrinsic loss parameter up to 8.49 nH m2 kgFe-1. The colloidal stability of the NFs was maintained when transferring to an aqueous solution via a simple ligand exchange protocol, replacing polyol ligands with biocompatible sodium tripolyphosphate to secure the IONPs long-term colloidal stabilization.

Small iron oxide nanoparticles as MRI T1 contrast agent: scalable inexpensive water-based synthesis using a flow reactor.

Small iron oxide nanoparticles (IONPs) were synthesised in water via co-precipitation by quenching particle growth after the desired magnetic iron oxide phase formed. This was achieved in a millifluidic multistage flow reactor by precisely timed addition of an acidic solution. IONPs (≤5 nm), a suitable size for positive T1 magnetic resonance imaging (MRI) contrast agents, were obtained and stabilised continuously. This novel flow chemistry approach facilitates a reproducible and scalable production, which is a crucial paradigm shift to utilise IONPs as contrast agents and replace currently used Gd complexes. Acid addition had to be timed carefully, as the inverse spinel structure formed within seconds after initiating the co-precipitation. Late quenching allowed IONPs to grow larger than 5 nm, whereas premature acid addition yielded undesired oxide phases. Use of a flow reactor was not only essential for scalability, but also to synthesise monodisperse and non-agglomerated small IONPs as (i) co-precipitation and acid addition occurred at homogenous environment due to accurate temperature control and rapid mixing and (ii) quenching of particle growth was possible at the optimum time, i.e., a few seconds after initiating co-precipitation. In addition to the timing of growth quenching, the effect of temperature and dextran present during co-precipitation on the final particle size was investigated. This approach differs from small IONP syntheses in batch utilising either growth inhibitors (which likely leads to impurities) or high temperature methods in organic solvents. Furthermore, this continuous synthesis enables the low-cost (<£10 per g) and large-scale production of highly stable small IONPs without the use of toxic reagents. The flow-synthesised small IONPs showed high T1 contrast enhancement, with transversal relaxivity (r2) reduced to 20.5 mM-1 s-1 and longitudinal relaxivity (r1) higher than 10 mM-1 s-1, which is among the highest values reported for water-based IONP synthesis.

Heat-Up Colloidal Synthesis of Shape-Controlled Cu-Se-S Nanostructures-Role of Precursor and Surfactant Reactivity and Performance in N2 Electroreduction.

Copper selenide-sulfide nanostructures were synthesized using metal-organic chemical routes in the presence of Cu- and Se-precursors as well as S-containing compounds. Our goal was first to examine if the initial Cu/Se 1:1 molar proportion in the starting reagents would always lead to equiatomic composition in the final product, depending on other synthesis parameters which affect the reagents reactivity. Such reaction conditions were the types of precursors, surfactants and other reagents, as well as the synthesis temperature. The use of 'hot-injection' processes was avoided, focusing on 'non-injection' ones; that is, only heat-up protocols were employed, which have the advantage of simple operation and scalability. All reagents were mixed at room temperature followed by further heating to a selected high temperature. It was found that for samples with particles of bigger size and anisotropic shape the CuSe composition was favored, whereas particles with smaller size and spherical shape possessed a Cu2-xSe phase, especially when no sulfur was present. Apart from elemental Se, Al2Se3 was used as an efficient selenium source for the first time for the acquisition of copper selenide nanostructures. The use of dodecanethiol in the presence of trioctylphosphine and elemental Se promoted the incorporation of sulfur in the materials crystal lattice, leading to Cu-Se-S compositions. A variety of techniques were used to characterize the formed nanomaterials such as XRD, TEM, HRTEM, STEM-EDX, AFM and UV-Vis-NIR. Promising results, especially for thin anisotropic nanoplates for use as electrocatalysts in nitrogen reduction reaction (NRR), were obtained.

Quantification of Lipoprotein Uptake in Vivo Using Magnetic Particle Imaging and Spectroscopy.

Lipids are a major source of energy for most tissues, and lipid uptake and storage is therefore crucial for energy homeostasis. So far, quantification of lipid uptake in vivo has primarily relied on radioactive isotope labeling, exposing human subjects or experimental animals to ionizing radiation. Here, we describe the quantification of in vivo uptake of chylomicrons, the primary carriers of dietary lipids, in metabolically active tissues using magnetic particle imaging (MPI) and magnetic particle spectroscopy (MPS). We show that loading artificial chylomicrons (ACM) with iron oxide nanoparticles (IONPs) enables rapid and highly sensitive post hoc detection of lipid uptake in situ using MPS. Importantly, by utilizing highly magnetic Zn-doped iron oxide nanoparticles (ZnMNPs), we generated ACM with MPI tracer properties superseding the current gold-standard, Resovist, enabling quantification of lipid uptake from whole-animal scans. We focused on brown adipose tissue (BAT), which dissipates heat and can consume a large part of nutrient lipids, as a model for tightly regulated and inducible lipid uptake. High BAT activity in humans correlates with leanness and improved cardiometabolic health. However, the lack of nonradioactive imaging techniques is an important hurdle for the development of BAT-centered therapies for metabolic diseases such as obesity and type 2 diabetes. Comparison of MPI measurements with iron quantification by inductively coupled plasma mass spectrometry revealed that MPI rivals the performance of this highly sensitive technique. Our results represent radioactivity-free quantification of lipid uptake in metabolically active tissues such as BAT.