Multivariate modulation of the Zr MOF UiO-66 for defect-controlled multimodal anticancer drug delivery

Metal‐organic frameworks (MOFs) are emerging as leading candidates for nanoscale drug delivery, as a consequence of their high drug capacities, ease of functionality, and the ability to carefully engineer key physical properties. Despite many anticancer treatment regimens consisting of a cocktail of different drugs, examples of delivery of multiple drugs from one MOF are rare, potentially hampered by difficulties in postsynthetic loading of more than one cargo molecule. Herein, we report a new strategy, multivariate modulation, which allows incorporation of up to three drugs in the Zr MOF UiO‐66 by defect‐loading. The drugs are added to one‐pot solvothermal synthesis and are distributed throughout the MOF at defect sites by coordination at the metal clusters. This tight binding comes with retention of crystallinity and porosity, allowing a fourth drug to be postsynthetically loaded into the MOFs to yield nanoparticles loaded with cocktails of drugs that show enhancements in selective anticancer cytotoxicity against MCF‐7 breast cancer cells in vitro. We believe that multivariate modulation is a significant advance in the application of MOFs in biomedicine, and anticipate the protocol will also be adopted in other areas of MOF chemistry, to easily produce defective MOFs with arrays of highly functionalised pores for potential application in gas separations and catalysis

Gadolinium Doped Layered Double Hydroxides for Simultaneous Drug Delivery and Magnetic Resonance Imaging

In this study, gadolinium (Gd) doped MgAl layered double hydroxides (LDHs) were synthesized via a ‘bottom-up’ method and fully characterized by X-ray diffraction, infrared spectroscopy and relaxivity measurements. Two cytotoxic agents were then intercalated via ion-exchange. X-ray diffraction patterns exhibit expanded interlayer spacings as a result of successful drug intercalation. Infrared spectra also showed characteristic peaks of the incorporated methotrexate (MTX) or 5-fluorouracil (5-FU). The LDHs were found to be highly stable under physiological conditions, while in acidic conditions a small proportion of Gd was freed into the immersion medium. Dissolution tests revealed that both 5FU and MTX were rapidly released from the LDH carrier. The longitudinal relaxivity of Gd-LDHs remains largely stable during drug release over 24 h, and was higher in acidic environments. Overall, the drug-loaded Gd-LDH systems prepared in this study could serve as pH-sensitive theranostic platforms for MRI-guided anti-cancer therapy.</p

Effect of lactation stage and concurrent pregnancy on milk composition in the bottlenose dolphin

Although many toothed whales (Cetacea: Odontoceti) lactate for 2–3 years or more, it is not known whether milk composition is affected by lactation stage in any odontocete species. We collected 64 pooled milk samples spanning 1–30 months postpartum from three captive bottlenose dolphins Tursiops truncatus. Milks were assayed for water, fat, crude protein (TN × 6.38) and sugar; gross energy was calculated. Ovulation and pregnancy were determined via monitoring of milk progesterone. Based on analysis of changes in milk composition for each individual dolphin, there were significant increases (P<0.05) in fat (in all three dolphins) and crude protein (in two of three), and a decrease (P<0.05) in water (in two of three) over the course of lactation, but the sugar content did not change. In all three animals, the energy content was positively correlated with month of lactation, but the percentage of energy provided by crude protein declined slightly but significantly (P<0.05). At mid-lactation (7–12 months postpartum, n=17), milk averaged 73.0±1.0% water, 12.8±1.0% fat, 8.9±0.5% crude protein, 1.0±0.1% sugar, 1.76±0.09 kcal g−1 (=7.25 kJ g−1) and 30.3±1.3% protein:energy per cent. This protein:energy per cent was surprisingly high compared with other cetaceans and in relation to the growth rates of calves. Milk progesterone indicated that dolphins ovulated and conceived between 413 and 673 days postpartum, following an increase in milk energy density. The significance of these observed compositional changes to calf nutrition will depend on the amounts of milk produced at different stages of lactation, and how milk composition and yield are influenced by sampling procedure, maternal diet and maternal condition, none of which are known

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe