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Solid-state 1H, 13C, and 15N nuclear magnetic resonance (NMR) spectroscopy has been an essential analytical method in studying complex molecules and biomolecules for decades. While oxygen-17 (17O) NMR is an ideal and robust candidate to study hydrogen bonding within secondary and tertiary protein structures for example, it continues to elude many. We discuss an improved multiple-turnover labeling procedure to develop a fast and cost-effective method to 17O label fluoroenylmethyloxycarbonyl (Fmoc)-protected amino acid building blocks. This approach allows for inexpensive ($0.25 USD/mg) insertion of 17O labels, an important barrier to overcome for future biomolecular studies. The 17O NMR results of these building blocks and a site-specific strategy for labeled N-acetyl-MLF-OH and N-formyl-MLF-OH tripeptides are presented. We showcase growth in NMR development for maximizing sensitivity gains using emerging sensitivity enhancement techniques including population transfer, high-field dynamic nuclear polarization, and cross-polarization magic-angle spinning cryoprobes.

All solid-state batteries offer the possibility of increased safety at potentially higher energy densities compared to conventional lithium-ion batteries. In an all-ceramic oxide battery, the composite cathode consists of at least one ion-conducting solid electrolyte and an active material, which are typically densified by sintering. In this study, the reaction of the solid electrolyte Li1.3Al0.3Ti1.7(PO4)3 (LATP) and the active material LiNi0.6Co0.2Mn0.2O2 (NCM622) is investigated by cosintering at temperatures between 550 and 650 °C. The characterization of the composites and the reaction layer is performed by optical dilatometry, X-ray diffractometry, field emission scanning electron microscopy with energy dispersive X-ray spectroscopy, time-of-flight secondary ion mass spectrometry, as well as scanning transmission electron microscopy (STEM). Even at low sintering temperatures, elemental diffusion occurs between the two phases, which leads to the formation of secondary phases and decomposition reactions of the active material and the solid electrolyte. As a result, the densification of the composite is prevented and ion-conducting paths between individual particles cannot be formed. Based on the experimental results, a mechanism of the reactions in cosintered LATP and NCM622 oxide composite cathodes is suggested.

To enable solid-state batteries with Li metal anodes, different classes of electrolytes are being investigated, mainly polymers, oxides, and sulfides. To overcome individual drawbacks of the material classes, so called bilayer hybrid cells combining layers of different electrolyte materials are considered highly promising. However, the introduction of an additional interface between the two solid electrolytes raises the question of the corresponding interfacial resistance. Herein, the properties of the interface between the two promising electrolytes Al-LLZO (Li6.16Al0.28La3Zr2O12) and LPS (Li7P3S11) are investigated by comprehensive impedance analyses. A series of systematic measurements allows to deconvolute the pressure dependence of the resistances related to the LPS material and the LPS/LLZO interface. This analysis reveals a significant pressure dependence of the LPS/LLZO interfacial resistance, mainly attributed to constriction resistance. Optimization of the LPS/LLZO interface is carried out by targeted surface treatment, resulting in a dramatic decrease of the interfacial resistance to virtually zero. These mechanistic studies and optimization approaches are complemented by practically relevant cycling tests using Li-metal electrodes. The cells show excellent cycling stability and negligible degradation. These findings contribute to the fundamental understanding of solid-solid interfaces in bilayer hybrid cells, indicating that solid-state batteries with hybrid LPS/LLZO electrolytes appear highly promising.

The present work studies the formation, chemical composition, and structure of an oxide layer formed on the technical solid-state sintered ceramic (EKasic®D) in a strong alkaline solution (1 M NaOH at pH 14) at high anodic potentials (30 V vs. 3 M Ag/AgCl). The observed formation of oxide films on SiC in alkaline solution is in contradiction to the thermodynamic laws (Pourbaix-diagram). The film thickness was determined by SEM/EDX measurements using the specific thin film analysis tool “AZtec” (Oxford Instruments) as well as the transmission electron microscopy. The thickness of the oxide film formed at 30 V amounts to 30 nm that corresponds with a field strength of E = 10 MV cm−1, which corresponds with the formation according to the high-field mechanism. The chemical composition was studied by EDX-analysis in a transmission electron microscope as well as by X-ray photoelectron spectroscopy (XPS). The oxide layer is completely amorphous and consists of non-stoichiometric SiOx and SiOxCy. The layer is assumed as graded with a higher amount of SiOx in the outermost regions and an increased amount of SiOxCy in the inner region of the passive layer. Additionally, the passive layer is doped by a small amount of aluminum originating from a sinter additive used in the manufacture of the SiC ceramic and completely incorporated into the SiC grains.

The evolution of the network connectivity of borosilicate glasses with the progressive addition of aluminum is analyzed using solid-state multinuclear magnetic resonance (NMR) spectroscopy to bette...

Electrochemical capacitors (ECs) have emerged as reliable and fast-charging electrochemical energy storage devices that offer high power densities. Their use is still limited, nevertheless, by thei...

The subtilase cytotoxin (SubAB) is secreted by certain Shiga toxin-producing Escherichia coli (STEC) strains and is composed of the enzymatically active subunit SubA and the pentameric binding/transport subunit SubB. We previously demonstrated that SubA (10 µg/ml), in the absence of SubB, binds and intoxicates the human cervix cancer-derived epithelial cell line HeLa. However, the cellular and molecular mechanisms underlying the cytotoxic activity of SubA in the absence of SubB remained unclear. In the present study, the cytotoxic effects mediated by SubA alone were investigated in more detail in HeLa cells and the human colon cancer cell line HCT116. We found that in the absence of SubB, SubA (10 µg/ml) is internalized into the endoplasmic reticulum (ER), where it cleaves the chaperone GRP78, an already known substrate for SubA after its canonical uptake into cells via SubB. The autonomous cellular uptake of SubA and subsequent cleavage of GRP78 in cells is prevented by treatment of cells with 10 µM brefeldin A, which inhibits the transport of protein toxins into the ER. In addition, by analyzing the SubA mutant SubAΔC344, we identified the C-terminal SEEL motif as an ER-targeting signal. Conclusively, our results strongly suggest that SubA alone shares the same intracellular transport route and cytotoxic activity as the SubAB holotoxin. Supplementary Information The online version contains supplementary material available at 10.1007/s00204-020-02965-2.

The first representative of a novel class of mixed-anionic compounds, the sulfate hydride Na3SO4H, and the corresponding deuteride Na3SO4D were obtained from the solid-state reaction of NaH or NaD with dry Na2SO4. Precise reaction control is required, because too harsh conditions lead to the reduction of sulfate to sulfide. A combined X-ray and neutron diffraction study revealed that the compound crystallizes in the tetragonal space group P4/nmm with the lattice parameters a=7.0034(2) Å and c=4.8569(2) Å. The sole presence of hydride and absence of hydroxide ions is proven by vibrational spectroscopy and comparison with spectra predicted from quantum chemical calculations. 1H and 23Na MAS NMR spectra are consistent with the structure of Na3SO4H: a single 1H peak at 2.9 ppm is observed, while two peaks at 15.0 and 6.2 ppm for the inequivalent 23Na sites are observed. Elemental analysis and quantum chemical calculations further support these results.

Die ersten Vertreter einer neuen Klasse gemischt‐anionischer Verbindungen, das Sulfathydrid Na3SO4H und das entsprechende Deuterid Na3SO4D, werden durch die Festkörperreaktion von NaH bzw. NaD mit trockenem Na2SO4 erhalten. Hierfür wird eine genaue Reaktionskontrolle benötigt, da zu harsche Reaktionsbedingungen zur Reduktion des Sulfats zum Sulfid führen. Eine kombinierte Auswertung von Röntgen‐ und Neutronendiffraktometrie zeigt, dass die Verbindung tetragonal mit der Raumgruppe P4/nmm und den Zellparametern a=7.0034(2) Å and c=4.8569(2) Å kristallisiert. Die alleinige Anwesenheit von Hydridionen und die Abwesenheit von Hydroxidionen wird durch Schwingungsspektroskopie im Vergleich zu Spektren, erhalten durch quantenchemische Berechnungen, bewiesen. 1H‐ und 23Na‐Festkörper‐NMR‐Spektren entsprechen der Struktur von Na3SO4H: ein 1H‐Signal bei 2.9 ppm sowie zwei Signale bei 15.0 und 6.2 ppm für zwei ungleiche 23Na‐Positionen. Zusätzlich stützen Elementaranalyse und quantenchemische Berechnungen die experimentellen Befunde.

Doped silicon nanocrystals (SiNCs) are promising materials that could find use in a wide variety of applications. Realizing methods to tailor the surface chemistry of these particles offers greater tunability of the material properties as well as broader solvent compatibility. Herein, we report organic-soluble B-doped SiNCs prepared via a thermal processing method followed by phosphorous pentachloride etching induced functionalization with alkoxy ligands of varied chain lengths. This approach provides a scalable route to solution processable B-doped SiNCs and establishes a potential avenue for the functionalization of other doped SiNCs.

Hybrid organic–inorganic metal-halide perovskite materials are an emerging class of materials that could profoundly change the optoelectronic and solar absorber research fields and have far-reachin...

The nucleoside analogue nelarabine, the prodrug of arabinosylguanine (AraG), is effective against T-cell acute lymphoblastic leukaemia (T-ALL) but not against B-cell ALL (B-ALL). The underlying mechanisms have remained elusive. Here, data from pharmacogenomics studies and a panel of ALL cell lines reveal an inverse correlation between nelarabine sensitivity and the expression of SAMHD1, which can hydrolyse and inactivate triphosphorylated nucleoside analogues. Lower SAMHD1 abundance is detected in T-ALL than in B-ALL in cell lines and patient-derived leukaemic blasts. Mechanistically, T-ALL cells display increased SAMHD1 promoter methylation without increased global DNA methylation. SAMHD1 depletion sensitises B-ALL cells to AraG, while ectopic SAMHD1 expression in SAMHD1-null T-ALL cells induces AraG resistance. SAMHD1 has a larger impact on nelarabine/AraG than on cytarabine in ALL cells. Opposite effects are observed in acute myeloid leukaemia cells, indicating entity-specific differences. In conclusion, SAMHD1 promoter methylation and, in turn, SAMHD1 expression levels determine ALL cell response to nelarabine., Rothenburger et al. combine the analysis of data from large pharmacogenomics screens with cell line experiments to elucidate mechanisms behind nelarabine resistance in acute lymphoblastic leukaemia (ALL). They identify low expression of the dNTP hydrolase SAMHD1 as a determinant of nelarabine sensitivity, suggesting the enzyme as a biomarker.

Diphtheria toxin (DT) efficiently inhibits protein synthesis in human cells, resulting in severe disease diphtheria. The sensitivity towards DT varies between mammalian species. Mice and rats are resistant to DT. However, the reason underlying this insensitivity is controversially discussed and not well understood. Therefore, we investigated the steps of DT uptake, i.e. receptor binding and internalization into mouse J774A.1 macrophages and primary rat fibroblasts. We exploited the non-toxic DT-mutant cross-reacting material 197 (CRM197) and three additional receptor binding-deficient mutants (250 nM each) to investigate binding to cell surface and internalization into murine cells via flow cytometry and stimulated emission depletion (STED) super-resolution optical microscopy. Dual-color STED imaging unveiled CRM197 interacting with the murine precursor of the heparin-binding epidermal growth factor-like growth factor (HB-EGF). Moreover, we identified CRM197’s transmembrane domain as an additional HB-EGF binding site, which is also involved in the receptor-mediated internalization into murine cells. However, we do not find evidence for translocation of the catalytically active subunit (DTA) into the cytosol when 250 nM DT were applied. In conclusion, we provide evidence that the resistance of murine cells to DT is caused by an insufficiency of DTA to escape from endosomes and reach the cytosol. Possibly, a higher affinity interaction of DT and the HB-EGF is required for translocation, which highlights the role of the receptor in the endosomes during the translocation step. We extend the current knowledge about cellular uptake of the medically relevant DT and CRM197. Electronic supplementary material The online version of this article (10.1007/s00204-020-02731-4) contains supplementary material, which is available to authorized users.

For cartilage repair in vivo or evaluation of new therapeutic approaches in vitro, the generation of functional cartilage tissue is of crucial importance and can only be achieved if the phenotype of the chondrocytes is preserved. Three-dimensional (3D) cell culture is broadly used for this purpose. However, adapting culture parameters like the oxygen tension or the osmolarity to their physiological values is often omitted. Indeed, articular cartilage is an avascular tissue subjected to reduced oxygen tension and presenting and increased osmolarity compared with most other tissues. In this study, we aimed at evaluating the effect of a physiological oxygen tension (3% instead of 21%) and physiological osmolarity (430 vs. 330 mOsm in nonadjusted DMEM) and the combination of both on the cell proliferation, matrix production, and the phenotype of porcine chondrocytes in a scaffold-free 3D culture system. We observed that a physiological osmolarity had no effect on cell proliferation and matrix production but positively influences the chondrocyte phenotype. A physiological oxygen level prevented cell proliferation but resulted in an increased matrix content/million cells and had a positive influence on the chondrocyte phenotype as well. The strongest benefit was reached with the combination of both physiological osmolarity and oxygen levels; with these conditions, type I collagen expression became undetectable. In addition, at 3% O2 the chondrocytes-matrix constructs were found to more closely resemble native cartilage regarding the matrix-to-cell ratio. In conclusion, this study clearly demonstrates the benefit of using physiological oxygen tension and osmolarity in cartilage tissue engineering with the combination of both showing the strongest benefit on the chondrocyte phenotype.

Microglia in the mediobasal hypothalamus (MBH) respond to inflammatory stimuli and metabolic perturbations to mediate body composition. This concept is well studied in the context of high fat diet induced obesity (HFDO), yet has not been investigated in the context of cachexia, a devastating metabolic syndrome characterized by anorexia, fatigue, and muscle catabolism. We show that microglia accumulate specifically in the MBH early in pancreatic ductal adenocarcinoma (PDAC)‐associated cachexia and assume an activated morphology. Furthermore, we observe astrogliosis in the MBH and hippocampus concurrent with cachexia initiation. We next show that circulating immune cells resembling macrophages infiltrate the MBH. PDAC‐derived factors induced microglia to express a transcriptional profile in vitro that was distinct from that induced by lipopolysaccharide (LPS). Microglia depletion through CSF1‐R antagonism resulted in accelerated cachexia onset and increased anorexia, fatigue, and muscle catabolism during PDAC. This corresponded with increased hypothalamic–pituitary–adrenal (HPA) axis activation. CSF1‐R antagonism had little effect on inflammatory response in the circulation, liver, or tumor. These findings demonstrate that microglia are protective against PDAC cachexia and provide mechanistic insight into this function., • Microgliosis occurs in the mediobasal hypothalamus early in pancreatic cancer.• Microglia respond to pancreatic cancer‐derived factors and produce arginase‐1.• Microglia depletion worsens cachexia during pancreatic cancer.

Polymer particles with antibody-like affinity, i.e., molecularly imprinted polymers, offer an ideal platform for biopharmaceutical virus purification. In recent years, attempts combining molecular imprinting technology with a variety of visualization and detection techniques have been reported for directly confirming the localized presence of the template. Direct target visualization is crucial for the characterization of molecularly imprinted polymers, especially if biological templates such as viruses are used. In the present study, for the first time the viral binding behavior at virus-imprinted polymers (VIPs) via stimulated emission depletion (STED) microscopy is shown by imaging individual, fluorescently labeled virus particles. STED microscopy achieves among various other super-resolution techniques the best temporal resolution at high spatial resolution. An innovative virus purification material selective for human adenovirus type 5 (AdV5) offered highly purified virus for the subsequent fluorescent labeling procedure, thus enabling STED imaging. Excellent binding affinities (150-fold higher versus control particles) and high selectivity toward the target virus (AdV5) were observed at those VIPs, even in competitive binding experiments with minute virus of mice using dual-label STED microscopy.

We report the synthesis of a bimetallic Rh(I) complex containing a bridging CO ligand that facilitates Rh–Rh bond formation. This bimetallic complex enables intramolecular allene hydroamination to form seven to ten-member rings in high yield. Monometallic Rh complexes, in contrast, fail to achieve any product formation. We demonstrate a broad substrate scope for formation of a variety of N-heterocycles in good to excellent yields. Macrocyclization reactions that form eleven to fifteen-membered heterocycles are also demonstrated. Mechanistic studies show that the reaction likely proceeds via catalyst protonation by trifluoroacetic acid, followed by reversible allene insertion and C–N bond-forming reductive elimination. The difference in product selectivity observed with our bimetallic catalyst vs monometallic Rh complexes may result from cooperativity between the two metals.

We study experimentally the propagation of nanosecond spin-wave pulses in microscopic waveguides made of nanometer-thick yttrium iron garnet films. For these studies, we use micro-focus Brillouin light scattering spectroscopy, which provides the possibility to observe propagation of the pulses with high spatial and temporal resolution. We show that, for most spin-wave frequencies, dispersion leads to broadening of the pulse by several times at propagation distances of 10 micrometers. However, for certain frequency interval, the dispersion broadening is suppressed almost completely resulting in a dispersionless pulse propagation. We show that the formation of the dispersion-free region is caused by the competing effects of the dipolar and the exchange interaction, which can be controlled by the variation of the waveguide geometry. These conclusions are supported by micromagnetic simulations and analytical calculations. Our findings provide a simple solution for the implementation of high-speed magnonic systems that require undisturbed propagation of short information-carrying spin-wave pulses.

Granulysin is an antimicrobial peptide (AMP) expressed by human T-lymphocytes and natural killer cells. Despite a remarkably broad antimicrobial spectrum, its implementation into clinical practice has been hampered by its large size and off-target effects. To circumvent these limitations, we synthesized a 29 amino acid fragment within the putative cytolytic site of Granulysin (termed “Gran1”). We evaluated the antimicrobial activity of Gran1 against the major human pathogen Mycobacterium tuberculosis (Mtb) and a panel of clinically relevant non-tuberculous mycobacteria which are notoriously difficult to treat. Gran1 efficiently inhibited the mycobacterial proliferation in the low micro molar range. Super-resolution fluorescence microscopy and scanning electron microscopy indicated that Gran1 interacts with the surface of Mtb, causing lethal distortions of the cell wall. Importantly, Gran1 showed no off-target effects (cytokine release, chemotaxis, cell death) in primary human cells or zebrafish embryos (cytotoxicity, developmental toxicity, neurotoxicity, cardiotoxicity). Gran1 was selectively internalized by macrophages, the major host cell of Mtb, and restricted the proliferation of the pathogen. Our results demonstrate that the hypothesis-driven design of AMPs is a powerful approach for the identification of small bioactive compounds with specific antimicrobial activity. Gran1 is a promising component for the design of AMP-containing nanoparticles with selective activity and favorable pharmacokinetics to be pushed forward into experimental in vivo models of infectious diseases, most notably tuberculosis.

Marine biomass waste is a remarkable source of functional molecules and materials. Yet material extraction, conversion and processing are often chemically intensive, preventing the widespread and clean use of these abundant resources for high-end applications. Moreover, current challenges in biomedicine call for the design of novel materials with better functional and mechanical properties. Herein, we present a novel chemical process to afford chitosan nanocrystals (ChsNCs), which uniquely combine a high degree of deacetylation, rod shape and high crystallinity for mechanical robustness. This method is a simple solid-state aging process starting from chitin nanocrystals (ChNCs) and requiring limited chemical and energetic input, which we have quantified using process mass intensity as the sustainability metric. This method, as well as a previously reported solution-based method, afforded a family of novel nanomaterials, which we used to form alginate hydrogels. The resulting materials are the first examples of ChsNC-based hydrogels and featured superior performances in terms of both rheological properties, as well as sustained drug release, as compared to previously reported chitosan/alginate systems. This work opens an avenue for functional soft materials using a green resource via a clean process.

SummaryBackgroundSAMHD1 mediates resistance to anti-cancer nucleoside analogues, including cytarabine, decitabine, and nelarabine that are commonly used for the treatment of leukaemia, through cleavage of their triphosphorylated forms. Hence, SAMHD1 inhibitors are promising candidates for the sensitisation of leukaemia cells to nucleoside analogue-based therapy. Here, we investigated the effects of the cytosine analogue CNDAC, which has been proposed to be a SAMHD1 substrate, in the context of SAMHD1.MethodsCNDAC was tested in 13 acute myeloid leukaemia (AML cell lines), in 26 acute lymphoblastic leukaemia cell lines, ten AML sublines adapted to various antileukaemic drugs, 24 single cell-derived clonal AML sublines, and primary leukaemic blasts from 24 AML patients. Moreover, 24 CNDAC-resistant sublines of the AML cell lines HL-60 and PL-21 were established. The SAMHD1 gene was disrupted using CRISPR/Cas9 and SAMHD1 depleted using RNAi, and the viral Vpx protein. Forced DCK expression was achieved by lentiviral transduction. SAMHD1 promoter methylation was determined by PCR after treatment of genomic DNA with the methylation-sensitive HpaII endonuclease. Nucleoside (analogue) triphosphate levels were determined by LC-MS/MS. CNDAC interaction with SAMHD1 was analysed by an enzymatic assay and by crystallisation.ResultsAlthough the cytosine analogue CNDAC was anticipated to inhibit SAMHD1, SAMHD1 mediated intrinsic CNDAC resistance in leukaemia cells. Accordingly, SAMHD1 depletion increased CNDAC triphosphate (CNDAC-TP) levels and CNDAC toxicity. Enzymatic assays and crystallisation studies confirmed CNDAC-TP to be a SAMHD1 substrate. In 24 CNDAC-adapted acute myeloid leukaemia (AML) sublines, resistance was driven by DCK (catalyses initial nucleoside phosphorylation) loss. CNDAC-adapted sublines displayed cross-resistance only to other DCK substrates (e.g. cytarabine, decitabine). Cell lines adapted to drugs not affected by DCK or SAMHD1 remained CNDAC sensitive. In cytarabine-adapted AML cells, increased SAMHD1 and reduced DCK levels contributed to cytarabine and CNDAC resistance.ConclusionIntrinsic and acquired resistance to CNDAC and related nucleoside analogues are driven by different mechanisms. The lack of cross-resistance between SAMHD1/ DCK substrates and non-substrates provides scope for next-line therapies after treatment failure.

We undertake steps to overcome four challenges that have hindered the understanding of ZnO/biomolecule interfaces at the atomic scale: parametrization of a classical force field, ZnO surface termination and amino acid protonation state in methanol, and convergence of enhanced sampling molecular dynamics simulations. We predict adsorption free energies for histidine, serine, cysteine, and tryptophan in remarkable agreement with experimental measurements obtained via a novel indicator-displacement assay. Adsorption is driven by direct surface/amino-acid interactions mediated by terminal hydroxyl groups and stabilized by strongly structured methanol solvation shells.

As a result of the high variability of fruit properties in the European plum Prunus domestica, a histochemical analysis of fruits at different stages of development was performed to understand the ripening process in cv. 'Colora' (yellow-red skinned) and cv. 'Topfive' (purple skinned). Histological analysis showed that carotenoids in the fruit had two different origins. In the fruit flesh, they derived from chloroplasts that turned into chromoplasts, whereas carotenoids in the fruit skin derived probably from proplastids. Flavan-3-ols and proanthocyanidins showed differential localization during ripening. They were visible in the vacuole in different fruit tissues or organized in tannosomes in the fruit flesh. Tanninoplasts were observed only in hypodermal cells of 'Colora'. Toward maturity, anthocyanins were detected in the epidermis and later in the hypodermis of both cultivars. The study forms a basis for the analysis of the biosynthesis of secondary metabolites in European plums and their biological effects.

Background: Nanoparticles are under investigation as carrier systems for anticancer drugs. The expression of efflux transporters such as the ATP-binding cassette (ABC) transporter ABCB1 is an important resistance mechanism in therapy-refractory cancer cells. Drug encapsulation into nanoparticles has been shown to bypass efflux-mediated drug resistance, but there are also conflicting results. To investigate whether easy-to-prepare nanoparticles made of well-tolerated polymers may circumvent transporter-mediated drug efflux, we prepared poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), and PEGylated PLGA (PLGA-PEG) nanoparticles loaded with the ABCB1 substrate doxorubicin by solvent displacement and emulsion diffusion approaches and assessed their anticancer efficiency in neuroblastoma cells, including ABCB1-expressing cell lines, in comparison to doxorubicin solution.Results: The resulting nanoparticles covered a size range between 73 and 246 nm. PLGA-PEG nanoparticle preparation by solvent displacement led to the smallest nanoparticles. In PLGA nanoparticles, the drug load could be optimised using solvent displacement at pH 7 reaching 53 µg doxorubicin/mg nanoparticle. These PLGA nanoparticles displayed sustained doxorubicin release kinetics compared to the more burst-like kinetics of the other preparations. In neuroblastoma cells, doxorubicin-loaded PLGA-PEG nanoparticles (presumably due to their small size) and PLGA nanoparticles prepared by solvent displacement at pH 7 (presumably due to their high drug load and superior drug release kinetics) exerted the strongest anticancer effects. However, nanoparticle-encapsulated doxorubicin did not display increased efficacy in ABCB1-expressing cells relative to doxorubicin solution.Conclusion: Doxorubicin-loaded nanoparticles made by different methods from different materials displayed substantial discrepancies in their anticancer activity at the cellular level. Optimised preparation methods resulted in PLGA nanoparticles characterised by increased drug load, controlled drug release, and high anticancer efficacy. The design of drug-loaded nanoparticles with optimised anticancer activity at the cellular level is an important step in the development of improved nanoparticle preparations for anticancer therapy. Further research is required to understand under which circumstances nanoparticles can be used to overcome efflux-mediated resistance in cancer cells.

An innovative application of metal-organic frameworks (MOFs) is in biomedical materials. To treat bone demineralization, which is a hallmark of osteoporosis, biocompatible MOFs (bioMOFs) have been proposed in which various components, such as alkaline-earth cations and bisphosphonate molecules, can be delivered to maintain normal bone density. Multicomponent bioMOFs that release several components simultaneously at a controlled rate thus offer an attractive solution. We report two new bioMOFs, comprising strontium and calcium ions linked by p-xylylenebisphosphonate molecules that release these three components and display no cytotoxic effects on human osteosarcoma cells. Varying the Sr2+/Ca2+ ratio in these bioMOFs causes the rate of ions dissolving into simulated body fluid to be unique; along with the ability to adsorb proteins, this property is crucial for future efforts in drug-release control and promotion of mineral formation. The one-pot synthesis of these bioMOFs demonstrates the utility of MOF design strategies.

The co-aromatization of methane with propane is investigated using Zn/HZSM-5 as the catalyst at 400 °C. The presence of methane has a pronounced effect on the product distribution in terms of improved formation of phenyl rings and substitution groups of aromatic species. Isotopic labeling and solid-state NMR spectroscopy studies reveal that the favored site for methane incorporation varies at different stages along the co-aromatization reaction, from the benzylic sites at the initial stage to the phenyl rings and then substitution groups as the reaction proceeds. SIMS spectroscopy of the involved reaction intermediates suggests the formation of C4 species over the Zn sites that are bonding to the oxygen atoms of the zeolite framework, which is supported by theoretical calculations. The interaction between Zn species and the zeolite framework is also confirmed by XAS and changes in coordination environments are identified through XANES and solid-state NMR spectroscopy. The redistribution of Zn during the reaction is observed on the surface of the zeolite support. Scanning transmission X-ray microscopy images show that Zn is rich in the inner pores compared with the external surface of the catalyst particles in the pristine catalysts. XANES and XPS spectra demonstrate that the Zn concentration increases on the external surface after the reaction, a conclusion that is further supported by the theoretical study. The Zn redistribution might be among the reasons for methane participation pathway alternation during the co-aromatization, since the Zn species located within the inner pores and on the external surface might prefer to catalyze the methane incorporation to the phenyl rings and substitution groups of the formed aromatics, respectively.