Photoluminescence of Argan-Waste-Derived Carbon Nanodots Embedded in Polymer Matrices.

In this work, photoluminescent (PL) carbon nano dots (CNDs) prepared from argan waste were embedded in highly optical transparent poly(styrene-co-acrylonitrile) (PSA) and cyclo-olefin copolymer (COC) matrices, which were further processed into thin films. In the first step, the luminescent CNDs were prepared through thermal processing of fine-groundargan waste, followed, in the second step, by direct dispersion in the polymer solutions, obtained by solving PSA and COC in selected solvents. These two polymer matrices were selected due to their high optical transparency, resilience to various environmental factors, and ability to be processed as quality thin films. The structural configuration of the CNDs was investigated through EDX, XPS, and FTIR, while DLS, HR-SEM, and STEM were used for their morphology investigation. The luminescence of the prepared CNDs and resulted polymer nanocomposites was thoroughly investigated through steady-state, absolute PLQY, and lifetime fluorescence. The quality of the resulted CND-polymer nanocomposite thin films was evaluated through AFM. The prepared highly luminescent thin films with a PL conversion efficiency of 30% are intended to be applied as outer photonic conversion layers on solar PV cells for increasing their conversion efficiency through valorization of the UV component of the solar radiation.

Targeted Cancer Therapy via pH-Functionalized Nanoparticles: A Scoping Review of Methods and Outcomes.

(1) Background: In recent years, several studies have described various and heterogenous methods to sensitize nanoparticles (NPs) to pH changes; therefore, in this current scoping review, we aimed to map current protocols for pH functionalization of NPs and analyze the outcomes of drug-loaded pH-functionalized NPs (pH-NPs) when delivered in vivo in tumoral tissue. (2) Methods: A systematic search of the PubMed database was performed for all published studies relating to in vivo models of anti-tumor drug delivery via pH-responsive NPs. Data on the type of NPs, the pH sensitization method, the in vivo model, the tumor cell line, the type and name of drug for targeted therapy, the type of in vivo imaging, and the method of delivery and outcomes were extracted in a separate database. (3) Results: One hundred and twenty eligible manuscripts were included. Interestingly, 45.8% of studies (n = 55) used polymers to construct nanoparticles, while others used other types, i.e., mesoporous silica (n = 15), metal (n = 8), lipids (n = 12), etc. The mean acidic pH value used in the current literature is 5.7. When exposed to in vitro acidic environment, without exception, pH-NPs released drugs inversely proportional to the pH value. pH-NPs showed an increase in tumor regression compared to controls, suggesting better targeted drug release. (4) Conclusions: pH-NPs were shown to improve drug delivery and enhance antitumoral effects in various experimental malignant cell lines.

Manganese-Doped N-Hydroxyphthalimide-Derived Carbon Dots-Theranostics Applications in Experimental Breast Cancer Models.

BACKGROUND: Theranostics, a novel concept in medicine, is based on the use of an agent for simultaneous diagnosis and treatment. Nanomaterials provide promising novel approaches to theranostics. Carbon Dots have been shown to exhibit anti-tumoral properties in various cancer models. The aim of the present study is to develop gadolinium, Fe3+, and Mn2+-doped N-hydroxyphthalimide-derived Carbon Dots. The resulted doped Carbon Dots should preserve the anti-tumoral properties while gaining magnetic resonance imaging properties. METHODS: Normal and cancer cell lines have been treated with doped Carbon Dots, and the cell viability has been measured. The doped Carbon Dots that exhibited the most prominent anti-tumoral effect accompanied by the lowest toxicity have been further in vivo tested. Magnetic resonance imaging evaluates both in vitro and in vivo the possibility of using doped Carbon Dots as a contrast agent. RESULTS: According to the results obtained from both the in vitro and in vivo experimental models used in our study, Mn2+-doped Carbon Dots (Mn-CDs-NHF) exhibit anti-tumoral properties, do not significantly impair the cell viability of normal cells, and reduce lung metastasis and the volume of mammary primary tumors while allowing magnetic resonance imaging. CONCLUSIONS: Our findings prove that Mn-CDs-NHF can be used as theranostics agents in pre-clinical models.

Hair EDX Analysis-A Promising Tool for Micronutrient Status Evaluation of Patients with IBD?

Micronutrient deficiencies can arise in various conditions, including inflammatory bowel diseases (IBD), and diagnosing these deficiencies can be challenging in the absence of specific clinical signs. The aim of this study was to evaluate the status of various trace elements hair concentration in IBD patients compared to a healthy control group and to identify potential correlations between the micronutrient status and relevant parameters related to disease activity. The concentrations of iron, magnesium, calcium, zinc, copper, manganese, selenium and sulfur in the hair of 37 IBD patients with prior diagnosed IBD (12 Crohn's disease and 25 ulcerative colitis) and 31 healthy controls were evaluated by Energy Dispersive X-Ray spectroscopy (EDX). Significant differences in hair concentration profile of studied trace elements were identified for IBD patients compared to healthy controls. A significantly decreased hair concentration of iron, magnesium, calcium and selenium and a significantly increased sulfur hair concentration were observed in IBD patients at the time of evaluation. A decreased hair calcium concentration (r = -0.772, p = 0.003) and an increased sulfur concentration (r = 0.585, p = 0.046) were significantly correlated with disease activity. Conclusion: Hair mineral and trace elements evaluation may contribute to a proper evaluation of their status in IBD patients and improving the management of nutritional status of IBD patients.

Raman Spectroscopy, X-ray Diffraction, and Scanning Electron Microscopy as Noninvasive Methods for Microstructural Alterations in Psoriatic Nails.

Psoriasis is a chronic inflammatory disease associated with immune system dysfunction that can affect nails, with a negative impact on patient life quality. Usually, nail psoriasis is associated with skin psoriasis and is therefore relatively simple to diagnose. However, up to 10% of nail psoriasis occurs isolated and may be difficult to diagnose by means of current methods (nail biopsy, dermoscopy, video dermoscopy, capillaroscopy, ultrasound of the nails, etc.). Since the nail is a complex biological tissue, mainly composes of hard α-keratins, the structural and morphological techniques can be used to analyze the human fingernails. The aim of this study was to corroborate the information obtained using Raman spectroscopy with those obtained by scanning electron microscopy (SEM) and X-ray diffractometry and to assess the potential of these techniques as non-invasive dermatologic diagnostic tools and an alternative to current methods.

SI-ATRP Decoration of Magnetic Nanoparticles with PHEMA and Post-Polymerization Modification with Folic Acid for Tumor Cells' Specific Targeting.

Targeted nanocarriers could reach new levels of drug delivery, bringing new tools for personalized medicine. It is known that cancer cells overexpress folate receptors on the cell surface compared to healthy cells, which could be used to create new nanocarriers with specific targeting moiety. In addition, magnetic nanoparticles can be guided under the influence of an external magnetic field in different areas of the body, allowing their precise localization. The main purpose of this paper was to decorate the surface of magnetic nanoparticles with poly(2-hydroxyethyl methacrylate) (PHEMA) by surface-initiated atomic transfer radical polymerization (SI-ATRP) followed by covalent bonding of folic acid to side groups of the polymer to create a high specificity magnetic nanocarrier with increased internalization capacity in tumor cells. The biocompatibility of the nanocarriers was demonstrated by testing them on the NHDF cell line and folate-dependent internalization capacity was tested on three tumor cell lines: MCF-7, HeLa and HepG2. It has also been shown that a higher concentration of folic acid covalently bound to the polymer leads to a higher internalization in tumor cells compared to healthy cells. Last but not least, magnetic resonance imaging was used to highlight the magnetic properties of the functionalized nanoparticles obtained.

NHF-derived carbon dots: prevalidation approach in breast cancer treatment.

Metastatic breast cancer dominates the female cancer-related mortality. Tumour-associated molecules represents a crucial for early disease detection and identification of novel therapeutic targets. Nanomaterial technologies provide promising novel approaches to disease diagnostics and therapeutics. In the present study we extend the investigations of antitumoral properties of Carbon Dots prepared from N-hydroxyphthalimide (CD-NHF) precursor. We evaluate the effect of CD-NHF on tumour cell migration and invasion in vitro and their impact on tumour progression using an in vivo model. Furthermore, we investigate the molecular mechanisms involved in CD-NHF antitumour effects. In vivo mammary tumours were induced in Balb/c female mice by injecting 4T1 cells into the mammary fat pad. Conditional treatment with CD-NHF significantly impair both migration and invasion of metastatic breast cancer cells. The presence of CD-NHF within the 3D cell cultures strongly inhibited the malignant phenotype of MDA-MB-231, 4T1 and MCF-7 cells in 3D culture, resulting in culture colonies lacking invasive projections and reduction of mammospheres formation. Importantly, breast tumour growth and metastasis dissemination was significantly reduced upon CD-NHF treatments in a syngeneic mouse model and is associated with down-regulation of Ki67 and HSP90 expression. CD-NHF nanostructures provide exciting perspective for improving treatment outcome in breast cancer.

Effect of TAT-DOX-PEG irradiated gold nanoparticles conjugates on human osteosarcoma cells.

The paper aims to investigate the cytotoxic effect on tumor cells of irradiated AuNPs in green light and subsequently functionalized with HS-PEG-NH2. The toxicity level of gold conjugates after their functionalization with DOX and TAT peptide was also evaluated. The AuNPs were prepared using the modified Turkevich method and exposed to visible light at a wavelength of 520 nm prior their PEGylation. The optical properties were analyzed by UV-vis spectroscopy, the surface modification was investigated using FTIR and XPS spectroscopies and their sizes and morphologies were evaluated by TEM and DLS techniques. DOX and TAT peptide were linked to the surface of PEGylated AuNPs by reacting their amino groups with glycidyloxypropyl of PEGylated DOX or TAT conjugates under mild conditions at room temperature and in the presence of ethanol as catalyst. The conjugates containing DOX or DOX and TAT have been characterized by fluorescence and FTIR techniques. The changes of electrochemical features were observed using cyclic voltammetry, suggesting a better stability of irradiated nanoparticles. By mass spectrometry it was confirmed that the compounds of interest were obtained. The cell viability test showed that irradiated and non-irradiated nanoparticles coated with PEG are not toxic in normal cells. Tumor cell viability analysis showed that the PEGylated nanoparticles modified with DOX and TAT peptide were more effective than pristine DOX, indicating cytotoxicity up to 10% higher than non-irradiated ones.

Probing the supramolecular features via π-π interaction of a di-iminopyrene-di-benzo-18-crown-6-ether compound: experimental and theoretical study.

A novel DPyDB-C[double bond, length as m-dash]N-18C6 compound was synthesised by linking a pyrene moiety to each phenyl group of dibenzo-18-crown-6-ether, the crown ether, through -HC[double bond, length as m-dash]N- bonds and characterized by FTIR, 1H-NMR, 13C-NMR, TGA, and DSC techniques. The quantitative 13C-NMR analysis revealed the presence of two position isomers. The electronic structure of the DPyDB-C[double bond, length as m-dash]N-18C6 molecule was characterized by UV-vis and fluorescence spectroscopies in four solvents with different polarities to observe particular behavior of isomers, as well as to demonstrate a possible non-bonding chemical association (such as ground- and excited-state associations, namely, to probe if there were forming dimers/excimers). The interpretation of the electronic structure was realized through QM calculations. The TD-CAM-B3LYP functional, at the 6-311+G(d,p) basis set, indicated the presence of predominant π → π* and mixed π → π* + n → π* transitions, in line with the UV-vis experimental data. Even though DPyDB-C[double bond, length as m-dash]N-18C6 computational studies revealed a π-extended conjugation effect with predominantly π → π* transitions, thorough fluorescence analysis was observed a weak emission, as an effect of PET and ACQ. In particular, the WAXD analysis of powder and thin films obtained from n-hexane, 1,2-dichloroethane, and ethanol indicated an amorphous organization, whereas from toluene a smectic ordering was obtained. These results were correlated with MD simulation, and it was observed that the molecular geometry of DPyDB-C[double bond, length as m-dash]N-18C6 molecule played a defining role in the pyrene stacking arrangement.

In Vitro and In Vivo Antioxidant Activity of the New Magnetic-Cerium Oxide Nanoconjugates.

BACKGROUND: Cerium oxide nanoparticles present the mimetic activity of superoxide dismutase, being able to inactivate the excess of reactive oxygen species (ROS) correlated with a large number of pathologies, such as stents restenosis and the occurrence of genetic mutations that can cause cancer. This study presents the synthesis and biological characterisation of nanoconjugates based on nanoparticles of iron oxide interconnected with cerium oxide conjugates. METHODS: The synthesis of magnetite-nanoceria nanoconjugates has been done in several stages, where the key to the process is the coating of nanoparticles with polyethyleneimine and its chemical activation-reticulation with glutaraldehyde. The nanoconjugates are characterised by several techniques, and the antioxidant activity was evaluated in vitro and in vivo. RESULTS: Iron oxide nanoparticles interconnected with cerium oxide nanoparticles were obtained, having an average diameter of 8 nm. Nanoconjugates prove to possess superparamagnetic properties and the saturation magnetisation varies with the addition of diamagnetic components in the system, remaining within the limits of biomedical applications. In vitro free-radical scavenging properties of nanoceria are improved after the coating of nanoparticles with polyethylenimine and conjugation with magnetite nanoparticles. In vivo studies reveal increased antioxidant activity in all organs and fluids collected from mice, which demonstrates the ability of the nanoconjugates to reduce oxidative stress. CONCLUSION: Nanoconjugates possess magnetic properties, being able to scavenge free radicals, reducing the oxidative stress. The combination of the two properties mentioned above makes them excellent candidates for theranostic applications.

Hyperpolarised NMR to follow water proton transport through membrane channels via exchange with biomolecules.

Water uptake in vesicles and the subsequent exchange between water protons and amide -NH protons in amino acids can be followed by a new, highly sensitive, type of magnetic resonance spectroscopy: dynamic nuclear polarisation (DNP)-enhanced NMR in the liquid state. Water hydrogen atoms are detected prior to and after their transfer to molecular sites in peptides and proteins featuring highly-accessible proton-exchangeable groups, as is the case for the -NH groups of intrinsically disordered proteins. The detected rates for amide proton-water proton exchange can be modulated by membrane-crossing rates, when a membrane channel is interposed. We hyperpolarised water proton spins via dynamic nuclear polarisation followed by sample dissolution (d-DNP) and transferred the created polarisation to -NH groups with high solvent accessibility in an intrinsically disordered protein domain. This domain is the membrane anchor of c-Src kinase, whose activity controls cell proliferation. The hindrance of effective water proton transfer rate constants observed in free solvent when a membrane-crossing step is involved is discussed. This study aims to assess the feasibility of recently-introduced hyperpolarised (DNP-enhanced) NMR to assess water membrane crossing dynamics.

Erosion as a possible mechanism for the decrease of size of plastic pieces floating in oceans.

A sea water wave tank fitted in an artificial UV light weathering chamber was built to study the behaviour of polypropylene (PP) injected pieces in close ocean-like conditions. In air, the same pieces sees a degradation in the bulk with a decrease of mechanical properties, a little change of crystal properties and nearly no change of surface chemistry. Weathering in the sea water wave tank shows only a surface changes, with no effect on crystals or mechanical properties with loss of small pieces of matter in the sub-micron range and a change of surface chemistry. This suggests an erosion dispersion mechanism. Such mechanism could explain why no particle smaller than about one millimeter is found when collecting plastic debris at sea: there are much smaller, eroded from plastic surfaces by a mechano-chemical process similar to the erosion mechanism found in the dispersion of agglomerate under flow.

Dynamic constitutional frameworks (DCFs) as nanovectors for cellular delivery of DNA.

We introduce Dynamic Constitutional Frameworks (DCFs), macromolecular structures that efficiently bind and transfect double stranded DNA. DCFs are easily synthesizable adaptive 3D networks consisting of core connection centres reversibly linked via labile imine bonds both to linear polyethyleneglycol (PEG, ∼1500 Da) and to branched polyethyleneimine (bPEI, ∼800 Da). DCFs bind linear and plasmid DNA, forming particulate polyplexes of 40-200 nm in diameter. The polyplexes are stable during gel electrophoresis, well tolerated by cells in culture, and exhibit significant transfection activity. We show that an optimal balance of PEG and bPEI components is important for building DCFs that are non-toxic and exhibit good cellular transfection activity. Our study demonstrates the versatility and effectiveness of DCFs as promising new vectors for DNA delivery.

Hybrid fullerene conjugates as vectors for DNA cell-delivery.

The present study reports fullerene conjugates that act as efficient binders of double stranded DNA (dsDNA) into cytofriendly polyplexes. The conjugates are designed to generate dendrimeric structures, having C60 as the core and bearing linear or branched PEI and polyethyleneglycol (PEG) arms (∼2 kDa). Simple and reproducible synthesis pathways provided C60-PEI and C60-PEG-PEI conjugates. They were able to bind linear and plasmidic dsDNA and they form particulate polyplexes of 50 to 200 nm in diameter. The resulted polyplexes toggle between the anionic and cationic state at nitrogen to phosphorous ratios (N/P) of about 5, as revealed by their zeta potential and became colloidally stable at N/P ratios above 10, as determined by atomic force microscopy (AFM). They are electrophoretically unbreakable starting with N/P ratios of 3 and of 5 when salmon sperm DNA and pEYFP-C1 plasmid, respectively are loaded. Both C60-PEI·pEYFP and C60-PEG-PEI·pEYFP polyplexes are non-cytotoxic against HEK 293T cells in culture and exhibit transfection efficiency better than 25% (N/P ratios above 20) and 6% (N/P ratios above 60) respectively, measured by flow cytometry. For comparison, the commercial SuperFect® from Qiagen (positive control) was able to provide an efficiency of 15-20%, under similar conditions. Moreover, the C60-PEG-PEI conjugate is as performant as the positive control in terms of expression of EYFP reporter gene in cultured cells and exhibited high cytocompatibility, determining cell proliferation up to 200%. Our study proved that C60-PEG-PEI is effective vector for DNA delivery being, in addition, easily synthesizable, practically non-cytotoxic and as efficient the commercially available transfection tools.

Heparin-anthranoid conjugates associated with nanomagnetite particles and their cytotoxic effect on cancer cells.

The paper describes a methodology for preparing monodisperse, water-soluble magnetite nanoparticles, coated with heparin and loaded with 4,5-dihydroxy-9,10-dioxoanthracene-2-carboxylic acid (Rhein), able to be used as a drug delivery system for cancer chemotherapy. Upon preparation, nanoparticles structure and morphology were investigated. The surface charge and the equivalent dimensions of the nanoparticles dispersed in water were measured, as a function of the suspension pH. The concentration of the drug into the nanoparticles shell, and the drug release profile was determined. The functionality of Rhein-loaded heparin-coated magnetic nanoparticles was assessed by monitoring their cytotoxic effect on cultured human tumor hepatocyte cell line, HepG2, using MTT assay. We found that upon exposure of HepG2 cells to Rhein-loaded heparin-coated nanoparticles, the cell viability was drastically reduced (to approximately 10%) as compared to that of the cells exposed to the free drug, indicating the potential of these magnetite nanoparticles to be used in cancer therapy.