Dominant frazil ice production in the Cape Darnley polynya leading to Antarctic Bottom Water formation.

Antarctic Bottom Water (AABW) occupies the abyssal layer of the world ocean and contributes to the global overturning circulation. It originates from dense shelf water, which forms from brine rejection during sea ice production. An important region of AABW formation has been identified off the Cape Darnley polynya. However, it remains unclear why and how high ice production leads to AABW formation. Using moored acoustic measurements and a satellite microwave algorithm, we reveal that underwater frazil ice dominates in the polynya. This underwater ice formation prevents heat-insulating surface-cover ice forming, thereby enabling efficient ice production. The high ice production in the nearshore and longer residence times create high-salinity source water for the AABW. Underwater frazil ice occurs as long as strong winds continue and occasionally penetrates depths of at least 80 m. Deep-penetrating frazil ice is particularly prominent in this polynya, while it also occurs in other Antarctic coastal polynyas.

A Dense Layer of Polyethyleneglycol and Zwitterionic Bone Targeting Peptide on the Surface of Stereocomplex Polylactide-Polyethyleneglycol Nanoparticles Improves Shelf-storage Stability and the Serum Compatibility.

The surface properties of nanoparticles (NPs) affect their stability and formation of the protein corona, which influence their targeting abilities. We evaluated these properties using bone (hydroxyapatite; HAP) targeting peptide on tamoxifen (TAM)-loaded stereocomplexformed polylactide-polyethyleneglycol (SC-PLA-PEG) NPs. Octaaspartic acid-octaglycine-cysteine (D8G8C) anionic derivative (Ani. pep.) and octa-aspartic acid-octa lysine-cysteine (D8K8C), a zwitterionic derivative (Zwi. pep.) were conjugated with SC-PLA-PEG NPs as HAP-targeting peptides. The addition of hydrophobic PLA homopolymers increased the surface PEG density on the NPs. Denser PEG chains on NPs decreased their specific surface area, reducing protein adsorption on the NPs and TAM release from NPs. NPs with dense PEG chains and Zwi. pep. showed superior shelf stability and lower protein adsorption than NPs with dense PEG chains and Ani. pep. in murine serum. Furthermore, the HAP-binding ability of NPs with Zwi. pep. was significantly higher than that of NPs with Ani. pep. These results indicate that decreasing the specific surface area and zwitterionization of HAP-targeting peptides on NPs are promising approaches to improve the serum compatibility and stability of NPs.

Orthogonal characterization and pharmacokinetic studies of polylactide-polyethyleneglycol polymeric nanoparticles with different physicochemical properties.

To optimize prolonged and sustained delivery of polylactide-block-polyethyleneglycol polymeric nanoparticles (PLA-PEG NPs), in terms of the PLA isomer and molecular weight, we performed orthogonal physicochemical characterization and evaluated the pharmacokinetics of tamoxifen (TAM)-loaded PLA-PEG NPs. DL-lactide- (DL-PEG NP), L-lactide- (L-PEG NPs), and stereocomplex-based (SC-PEG NPs) PLA-PEGs, with two different PLA to PEG ratios (12k-5k and 5k-5k Da) were synthesized, and NPs were prepared by anti-solvent precipitation. Size exclusion chromatography, multi-angle light scattering, dynamic light scattering, and 1H nuclear magnetic resonance studies revealed that SC-PEG NPs (12k-5k) had a compact structure and the highest PEG density, followed by L-PEG NPs (12k-5k), DL-PEG NPs (12k-5k), and all PLA-PEG NPs (5k-5k). Additionally, solid-phase extraction indicated that SC-PEG NPs (12k-5k) had the highest drug loading content and the lowest surface TAM adsorption, of the PLA-PEGs evaluated. These results were explained by the crystallinity of the PLA core, which was analyzed by X-ray diffraction. In the pharmacokinetic studies, 14C-TAM-loaded 111In-SC-PEG NPs (12k-5k) exhibited the highest area under the plasma concentration-time curve, followed by L-PEG NPs (12k-5k) and DL-PEG NPs (12k-5k), after intravenous injection in mice. These results indicate that SC-PEG NPs (12k-5k) are promising drug carriers for the sustained and prolonged delivery of TAM.

Production of Dibromomethane and Changes in the Bacterial Community in Bromoform-Enriched Seawater.

The responses of bacterial communities to halocarbon were examined using a 28-d incubation of bromoform- and methanol-enriched subarctic surface seawater. Significant increases were observed in dibromomethane concentrations and bacterial 16S rRNA gene copy numbers in the treated substrates incubated for 13 d. The accumulated bacterial community was investigated by denaturing gradient gel electrophoresis and amplicon analyses. The dominant genotypes corresponded to the genera Roseobacter, Lentibacter, and Amylibacter; the family Flavobacteriaceae; and the phylum Planctomycetes, including methylotrophs of the genus Methylophaga and the family Methylophilaceae. Therefore, various phylotypes responded along with the dehalogenation processes in subarctic seawater.

Development of orally-deliverable DNA hydrogel by microemulsification and chitosan coating.

Self-gelling DNA hydrogels with cytosine-phosphate-guanine (CpG) motifs have been shown to exhibit high potency as vaccine adjuvants. However, their oral use is limited because of their thermodynamic and chemical instability in the gastrointestinal tract. In this study, we aimed to develop DNA hydrogel microspheres (Dgel-MS) coated with chitosan to improve their stability. Chitosan-coated Dgel-MS (Cs-Dgel-MS) was prepared by emulsifying Dgel to obtain the D-gel core, followed by mixing with microemulsions of chitosan for electrostatic coating. Fluorescence imaging of Cs-Dgel-MS labeled with fluorescent dyes showed that Dgel-MS (approximately 30 µm) was coated with chitosan. The recovery efficiency of Alexa Fluor 488-DNA was 87.4 ±â€¯7.5%. To load a phosphorothioate CpG oligodeoxynucleotide into Dgel, a modified Dgel (mDgel) was designed and fluorescein isothiocyanate (FITC)-dextran was loaded into Cs-mDgel-MS as a model compound. The recovery efficiency of Alexa Fluor 488-CpG1668 and FITC-dextran was 83.3 ±â€¯3.8% and 67.8 ±â€¯4.6%, respectively. The release of Alexa Fluor 488-CpG1668 from Cs-mDgel-MS was slower than that from mDgel under acidic or DNase conditions. Intra-duodenal administration of FITC-dextran/Cs-mDgel-MS showed prolonged intestinal transition of the encapsulated FITC-dextran. These results indicate that Cs-Dgel-MS can be useful for oral delivery of CpG DNA and other bioactive compounds.

Construction of nanostructured DNA harbouring phosphorodiamidate morpholino oligonucleotide for controlled tissue distribution in mice.

Phosphorodiamidate morpholino oligonucleotides (PMOs) are a class of antisense oligonucleotides used in the treatment of neuromuscular diseases. Their major drawbacks are high blood clearance and poor cellular delivery. Previously, we demonstrated that tripod-like nanostructured DNA, or tripodna, was efficiently taken up by macrophages and dendritic cells. In this study, we used iodine-125(125I)-labelled PMOs, designed a tripodna harbouring an 125I-PMO (125I-PMO/tripodna), and evaluated whether this tripodna could control the pharmacokinetic properties of PMO. Gel electrophoresis showed that 125I-PMO was almost completely incorporated into the tripodna. Compared to 125I-PMO, 125I-PMO/tripodna was more efficiently taken up by macrophage-like RAW264.7 cells. Moreover, after intravenous injection into mice, the area under the plasma concentration-time curve of 125I-PMO/tripodna was significantly larger than that of 125I-PMO. The distribution of 125I-PMO/tripodna in the liver and spleen at 24 h was 32- and 51-fold higher than that of 125I-PMO, respectively. The fractionation of liver cells revealed that non-parenchymal cells were the major cells contributing to the hepatic uptake of 125I-PMO/tripodna. These results indicate that tripodna has the potential to deliver PMO, particularly to the liver and spleen.