Synthesis and functionalisation of superparamagnetic nano-rods towards the treatment of glioblastoma brain tumours

The complete removal of glioblastoma brain tumours is impossible to achieve by surgery alone due to the complex finger-like tentacle structure of the tumour cells and their migration away from the bulk of the tumour at the time of surgery; furthermore, despite aggressive chemotherapy and radiotherapy treatments following surgery, tumour cells continue to grow, leading to the death of patients within 15 months after diagnosis. The naturally occurring carnosine dipeptide has previously demonstrated activity against in vitro cultured glioblastoma cells; however, at natural physiological concentrations, its activity is too low to have a significant effect. Towards realising the full oncological potential of carnosine, the dipeptide was embedded within an externally triggered carrier, comprising a novel nano rod-shaped superparamagnetic iron oxide nanoparticle (ca. 86 × 19 × 11 nm) capped with a branched polyethyleneimine, which released the therapeutic agent in the presence of an external magnetic field. The new nano-carrier was characterized using electron microscopy, dynamic light scattering, elemental analysis, and magnetic resonance imaging techniques. In addition to cytotoxicity studies, the carnosine carrier’s effectiveness as a treatment for glioblastoma was screened in vitro using the U87 human glioblastoma astrocytoma cell line. The labile carnosine (100 mM) suppresses both the U87 cells’ proliferation and mobility over 48 h, resulting in significant reduction in migration and potential metastasis. Carnosine was found to be fully released from the carrier using only mild hyperthermia conditions (40 °C), facilitating an achievable clinical application of the slow, sustained-release treatment of glioblastoma brain tumours that demonstrates potential to inhibit post-surgery metastasis with the added benefit of non-invasive monitoring via MRI

Controlled release of carnosine from poly(lactic-co-glycolic acid) beads using nanomechanical magnetic trigger towards the treatment of glioblastoma

Nanometer scale rods of superparamagnetic iron oxide have been encapsulated, along with the anti-cancer therapeutic carnosine, inside porous poly(lactic-co-glycolic acid) microbeads with a uniform morphology, synthesised using microfluidic arrays. The sustained and externally triggered controlled release from these vehicles was demonstrated using a rotating Halbach magnet array, quantified via liquid chromatography, and imaged in situ using magnetic resonance imaging (MRI) and scanning electron microscopy (SEM). In the absence of the external magnetic trigger, the carnosine was found to be released from the polymer in a linear profile; however, over 50% of the drug could be released within 30 minutes of exposure to the rotating magnetic field. In addition, the release of carnosine embedded on the surface of the nano-rods was delayed if it was mixed with the iron oxide nano rods before the encapsulation. These new drug delivery vesicles have the potential to pave the way towards the safe and triggered release of onsite drug delivery, as part of a theragnostic treatment for glioblastoma

Ethylene glycol coated nanoceria protects against oxidative stress in human lens epithelium

Chronic diseases are rising in incidence and prevalence because of increases in life expectancy in many parts of the world coupled with advances in medicine which manage disease progression, rather than curing and alleviating the causes. Cataract is one such chronic condition. Identifying a therapeutic intervention that is successful in reversing or preventing cataracts may have applications for other chronic diseases of protein misfolding, such as diabetes and Alzheimer's disease as these have similar causation factors, notably oxidative stress and/or glycation. Cerium oxide nanoparticles (nanoceria) which have antioxidant, radioprotective and enzyme-mimetic properties have the potential to lead to an effective non-surgical treatment. However, nanoceria stability in physiological media is poor thus hindering their effective use in biomedical applications. Here we report a highly efficient one-pot synthesis of nanoceria (2–5 nm) coated with ethylene glycol, that is colloidally stable in physiological media and exhibits multiwavelength photoluminescence. The formulation, up to concentrations of 200 μg ml−1, was not toxic to human lens epithelial cells and had no adverse effect on the cellular morphology or proliferation rate. More significantly, these nanoceria showed protective effects against oxidative stress induced by hydrogen peroxide in lens epithelial cells. Electron microscopy studies show the internalization and cytoplasmic localization of the nanoceria was found to be largely in the perinuclear region

Nematocidal effects of a coriander essential oil and five pure principles on the infective larvae of major ovine gastrointestinal nematodes in vitro

The anthelmintic effects of extracted coriander oil and five pure essential oil constituents (geraniol, geranyl acetate, eugenol, methyl iso-eugenol, and linalool) were tested, using larval motility assay, on the third-stage larvae (L3s) of Haemonchus contortus, Trichostrongylus axei, Teladorsagia circumcincta, Trichostrongylus colubriformis, Trichostrongylus vitrinus and Cooperia oncophora. Coriander oil and linalool, a major component of tested coriander oil, showed a strong inhibitory efficacy against all species, except C. oncophora with a half maximal inhibitory concentration (IC50) that ranged from 0.56 to 1.41% for the coriander oil and 0.51 to 1.76% for linalool. The coriander oil and linalool combinations conferred a synergistic anthelmintic effect (combination index [CI] <1) on larval motility comparable to positive control (20 mg/mL levamisole) within 24 h (p < 0.05), reduced IC50 values to 0.11–0.49% and induced a considerable structural damage to L3s. Results of the combined treatment were validated by quantitative fluorometric microplate-based assays using Sytox green, propidium iodide and C12-resazurin, which successfully discriminated live/dead larvae. Only Sytox green staining achieved IC50 values comparable to that of the larval motility assay. The cytotoxicity of the combined coriander oil and linalool on Madin–Darby Canine Kidney cells was evaluated using sulforhodamine-B (SRB) assay and showed no significant cytotoxic effect at concentrations < 1%. These results indicate that testing essential oils and their main components may help to find new potential anthelmintic compounds, while at the same time reducing the reliance on synthetic anthelmintics

Design and testing of microbubble‐based MRI contrast agents for gastric pressure measurement

Purpose: This work demonstrates specifically tailored microbubble‐based preparations and their suitability as MRI contrast agents for ingestion and measuring temporal and spatial pressure variation in the human stomach. Methods: Enhanced alginate spheres were prepared by incorporating gas‐filled microbubbles into sodium alginate solution followed by the polymerization of the mixture in an aqueous calcium lactate solution. The microbubbles were prepared with a phospholipid shell and perfluorocarbon gas filling, using a mechanical cavitational agitation regime. The NMR signal changes to externally applied pressure and coming from the enhanced alginate spheres were acquired and compared with that of alginate spheres without microbubbles. In vivo investigations were also carried out on healthy volunteers to measure the pressure variation in the stomach. Results: The MR signal changes in the contrast agent exhibits a linear sensitivity of approximately 40% per bar, as opposed to no measurable signal change seen in the control gas‐free spheres. This novel contrast agent also demonstrates an excellent stability in simulated gastric conditions, including at body temperature. In vivo studies showed that the signal change exhibited in the meal within the antrum region is between 5% and 10%, but appears to come from both pressure changes and partial volume artifacts. Conclusion: This study demonstrates that alginate spheres with microbubbles can be used as an MRI contrast agent to measure pressure changes. The peristaltic movement within the stomach is seen to substantially alter the overall signal intensity of the contrast agent meal. Future work must focus on improving the contrast agent's sensitivity to pressure changes

Bioavailability of methionine-coated zinc nanoparticles as a dietary supplement leads to improved performance and bone strength in broiler chicken production

Recently, nanotechnology has been widely adopted in many fields. The goal of this study was to evaluate the potential for amino acid coated nano minerals as a supplement in broiler feed. Zinc was selected as a model mineral for this test and supplementation of nano zinc, both coated and uncoated was compared with organic and inorganic commercial forms of zinc. A total of 48 pens (8 birds each) were assigned to one of the following dietary treatments: Control, methionine-Zinc chelate (M-Zn), nano zinc oxide (Nano-ZnO), and methionine coated nano zinc oxide (M-Nano-ZnO). All experimental diets were formulated with the same total zinc, methionine, protein, and energy content with just the zinc source as a variable. Bird weight, feed intake and feed conversion ratios were recorded weekly, with three birds culled (sacrificed) at day 21 and day 35 for sampling measures. Ileal digestibility of zinc was determined at day 21 and day 35 using titanium dioxide as an inert marker. Blood serum, liver and spleen samples were collected at day 21 and day 35 and analysed for zinc content via inductively coupled plasma mass spectrometry (ICP-MS). Tibia strength and morphometrics were measured from both legs of three birds per pen at day 21 and day 35. The study was conducted at Nottingham Trent University Poultry Unit, UK. The novel method of producing nano minerals coated with amino acids was successfully tested with zinc and material produced to test in the feeding study. Methionine coated nano zinc oxide supplementation significantly improved bird weight gain and the increased feed intake of broilers compared to an inorganic zinc form. Ileal digestibility was also improved with this methionine-nano zinc. Moreover, this supplementation improved the tibia strength of broilers at the age of 21 days, though this was not observed at day 35. Therefore, M-Nano-ZnO could be used to supplement broilers to improve both performance and digestibility with a limited positive impact on bone strength. The results of the current study suggest that the amino acid coating of nano minerals can improve the digestibility of minerals which may have further implications for the field of mineral nutrition in animal feeds

Vaterite-nanosilver hybrids with antibacterial properties and pH-triggered release

Silver nanoparticles (AgNPs) have been used for over a century in various applications due to their distinctive properties. Nonetheless, the poor stability of AgNPs and adverse effects on living organisms have driven the search for materials able to protect and better control their release. Vaterite CaCO3 crystals have been studied in the last two decades as carriers for different drugs due to their biocompatibility, easy synthesis and pH-sensitive properties. Herein, AgNPs were loaded into vaterite to protect, store, and control their release, resulting in CaCO3/AgNPs hybrids. To tune the release of the AgNPs, the recrystallization of the hybrids into thermodynamically more stable calcite was studied and modulated with carboxymethyledextran (DexCM) and poly(4-styrenesulfonic acid) sodium salt (PSS), with the last one being able to stabilise the hybrids and prevent a premature release of the AgNPs at low contents (2%, w/w). The release of AgNPs from the hybrids was studied at pH 5 to 9, showing a pH-dependent release suppression for PSS-stabilised hybrids. Various mathematical models were applied to clarify the release mechanism, confirming the role of PSS in stabilising and targeting the release of AgNPs. The antibacterial studies demonstrated that the hybrids protect the AgNPs without affecting their activity, with the released nanoparticles being effective against Escherichia coli, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Overall, this work sheds light on the release mechanisms of AgNPs from the inorganic hybrids helping to foresee the release profiles of other compounds from vaterite

Silica bound co-pillar[4+1]arene as a novel supramolecular stationary phase

A novel co-pillar[4+1]arene incorporating two bromo-octyl substituents has been synthesised for the first time, using microwave irradiation in high yield (88%) in under four minutes, and bound to the surface of chromatographic silica particles. The resulting new stationary phase has been successfully utilised to separate xylene isomers via liquid chromatographic techniques