Micro-syringe chip-guided intratumoral administration of lipid nanoparticles for targeted anticancer therapy.

BACKGROUND: Nano-sized drug delivery system has been widely studied as a potential technique to promote tumor-specific delivery of anticancer drugs due to its passive targeting property, but resulting in very restricted improvements in its systemic administration so far. There is a requirement for a different approach that dramatically increases the targeting efficiency of therapeutic agents at targeted tumor tissues. METHODS: To improve the tumor-specific accumulation of anticancer drugs and minimize their undesirable toxicity to normal tissues, a tumor-implantable micro-syringe chip (MSC) with a drug reservoir is fabricated. As a clinically established delivery system, six liposome nanoparticles (LNPs) with different compositions and surface chemistry are prepared and their physicochemical properties and cellular uptake are examined in vitro. Subsequently, MSC-guided intratumoral administration is studied to identify the most appropriate for the higher tumor targeting efficacy with a uniform intratumoral distribution. For efficient cancer treatment, pro-apoptotic anticancer prodrugs (SMAC-P-FRRG-DOX) are encapsulated to the optimal LNPs (SMAC-P-FRRG-DOX encapsulating LNPs; ApoLNPs), then the ApoLNPs are loaded into the 1 µL-volume drug reservoir of MSC to be delivered intratumorally for 9 h. The tumor accumulation and therapeutic effect of ApoLNPs administered via MSC guidance are evaluated and compared to those of intravenous and intratumoral administration of ApoLNP in 4T1 tumor-bearing mice. RESULTS: MSC is precisely fabricated to have a 0.5 × 4.5 mm needle and 1 µL-volume drug reservoir to achieve the uniform intratumoral distribution of LNPs in targeted tumor tissues. Six liposome nanoparticles with different compositions of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (PC), 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (PS), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)2000] (PEG2000-DSPE) are prepared with average sizes of 100-120 nm and loaded into the 1 µL-volume drug reservoir in MSC. Importantly negatively charged 10 mol% of PS-containing LNPs are very slowly infused into the tumor tissue through the micro-syringe of the MSC over 6 h. The intratumoral targeting efficiency of MSC guidance is 93.5%, effectively assisting the homogeneous diffusion of LNPs throughout the tumor tissue at 3.8- and 2.7-fold higher concentrations compared to the intravenous and intratumoral administrations of LNPs, respectively. Among the six LNP candidates 10 mol% of PS-containing LNPs are finally selected for preparing pro-apoptotic SMAC-P-FRRG-DOX anticancer prodrug-encapsulated LNPs (ApoLNPs) due to their moderate endocytosis rate high tumor accumulation and homogenous intratumoral distribution. The ApoLNPs show a high therapeutic effect specifically to cathepsin B-overexpressing cancer cells with 6.6 µM of IC50 value while its IC50 against normal cells is 230.7 µM. The MSC-guided administration of ApoLNPs efficiently inhibits tumor growth wherein the size of the tumor is 4.7- and 2.2-fold smaller than those treated with saline and intratumoral ApoLNP without MSC, respectively. Moreover, the ApoLNPs remarkably reduce the inhibitor of apoptosis proteins (IAPs) level in tumor tissues confirming their efficacy even in cancers with high drug resistance. CONCLUSION: The MSC-guided administration of LNPs greatly enhances the therapeutic efficiency of anticancer drugs via the slow diffusion mechanism through micro-syringe to tumor tissues for 6 h, whereas they bypass most hurdles of systemic delivery including hepatic metabolism, rapid renal clearance, and interaction with blood components or other normal tissues, resulting in the minimum toxicity to normal tissues. The negatively charged ApoLNPs with cancer cell-specific pro-apoptotic prodrug (SMAC-P-FRRG-DOX) show the highest tumor-targeting efficacy when they are treated with the MSC guidance, compared to their intravenous or intratumoral administration in 4T1 tumor-bearing mice. The MSC-guided administration of anticancer drug-encapsulated LNPs is expected to be a potent platform system that facilitates overcoming the limitations of systemic drug administration with low delivery efficiency and serious side effects.

Molecular Dipoles as a Surface Flattening and Interface Stabilizing Agent for Lithium-Metal Batteries.

Reaching the border of the capable energy limit in existing battery technology has turned research attention away from the rebirth of unstable Li-metal anode chemistry in order to achieve exceptional performance. Strict regulation of the dendritic Li surface reaction, which results in a short circuit and safety issues, should be achieved to realize Li-metal batteries. Herein, this study reports a surface-flattening and interface product stabilizing agent employing methyl pyrrolidone (MP) molecular dipoles in the electrolyte for cyclable Li-metal batteries. The excellent stability of the Li-metal electrode over 600 cycles at a high current density of 5 mA cm-2 has been demonstrated using an optimal concentration of the MP additive. This study has identified the flattening surface reconstruction and crystal rearrangement behavior along the stable (110) plane assisted by the MP molecular dipoles. The stabilization of the Li-metal anodes using molecular dipole agents has helped develop next-generation energy storage devices using Li-metal anodes, such as Li-air, Li-S, and semi-solid-state batteries.

A Reflection on Sustainable Anode Materials for Electrochemical Chloride Oxidation.

Chloride oxidation is a key industrial electrochemical process in chlorine-based chemical production and water treatment. Over the past few decades, dimensionally stable anodes (DSAs) consisting of RuO2 - and IrO2 -based mixed-metal oxides have been successfully commercialized in the electrochemical chloride oxidation industry. For a sustainable supply of anode materials, considerable efforts both from the scientific and industrial aspects for developing earth-abundant-metal-based electrocatalysts have been made. This review first describes the history of commercial DSA fabrication and strategies to improve their efficiency and stability. Important features related to the electrocatalytic performance for chloride oxidation and reaction mechanism are then summarized. From the perspective of sustainability, recent progress in the design and fabrication of noble-metal-free anode materials, as well as methods for evaluating the industrialization of novel electrocatalysts, are highlighted. Finally, future directions for developing highly efficient and stable electrocatalysts for industrial chloride oxidation are proposed.

Understanding the Flame Retardant Mechanism of Intumescent Flame Retardant on Improving the Fire Safety of Rigid Polyurethane Foam.

Combinations of multiple inorganic fillers have emerged as viable synergistic agents for boosting the flame retardancy of intumescent flame retardant (IFR) polymer materials. However, few studies on the effect of multiple inorganic fillers on the flame retardant behavior of rigid polyurethane (RPU) foam have been carried out. In this paper, a flame retardant combination of aluminum hydroxide (ATH) and traditional flame retardants ammonium polyphosphate (APP), pentaerythritol (PER), melamine cyanurate (MC), calcium carbonate (CC), and expandable graphite (EG) was incorporated into RPU foam to investigate the synergistic effects of the combination of multiple IFR materials on the thermal stability and fire resistance of RPU foam. Scanning electron microscopy (SEM) and thermogravimetric analysis (TGA) revealed that 8 parts per hundred polyols by weight (php) filler concentrations were compatible with RPU foam and yielded an increased amount of char residue compared to the rest of the RPU samples. The flame retardancy of multiple fillers on intumescent flame retardant RPU foam was also investigated using cone calorimeter (CCTs) and limiting oxygen index (LOI) tests, which showed that RPU/IFR1 (APP/PER/MC/EG/CC/ATH) had the best flame retardant performance, with a low peak heat release rate (PHRR) of 82.12 kW/m2, total heat release rate (THR) of 15.15 MJ/m2, and high LOI value of 36%. Furthermore, char residue analysis revealed that the use of multiple fillers contributed to the generation of more intact and homogeneous char after combustion, which led to reduced decomposition of the RPU foam and hindered heat transfer between the gas and condensed phases.

Microcapsule-Type Self-Healing Protective Coating That Can Maintain Its Healed State upon Crack Expansion.

The purpose of this study was to develop a microcapsule-type self-healing coating system that could self-heal cracks and then maintain the healed state even upon crack expansion. Mixtures consisting of a photoinitiator and two methacrylate components, bismethacryloxypropyl-terminated polydimethylsiloxane (BMT-PDMS) and monomethacryloxypropyl-terminated PDMS (MMT-PDMS), were transformed into viscoelastic semi-solids through photoreaction. The viscoelasticity of the reacted mixtures could be controlled by varying the mass ratio of the two methacrylates. Through a stretchability test, the optimal composition mixture was chosen as a healing agent. Microcapsules loaded with the healing agent were prepared and dispersed in a commercial undercoating to obtain a self-healing coating formulation. The formulation was applied onto mortar specimens, and then cracks were generated in the coating by using a universal testing machine (UTM). Cracks with around a 150-µm mean width were generated and were allowed to self-heal under UV light. Then, the cracks were expanded up to 650 µm in width. By conducting a water sorptivity test at each expanded crack width, the self-healing efficiency and capability of maintaining the healed state were evaluated. The B-M-1.5-1-based coating showed a healing efficiency of 90% at a 150-µm crack width and maintained its healing efficiency (about 80%) up to a 350-µm crack width. This self-healing coating system is promising for the protection of structural materials that can undergo crack formation and expansion.

Effect of Enhanced Recovery After Surgery program on hospital stay and 90-day readmission after pancreaticoduodenectomy: a single, tertiary center experience in Korea.

PURPOSE: Despite increasing number of reports on Enhanced Recovery After Surgery program (ERAS) and readmission after pancreaticoduodenectomy (PD) from Western countries, there are very few reports on this topic from Asian countries. This study aimed to evaluate the effects of ERAS on hospital stay and readmission and to identify reasons and risk factors for readmission after PD. METHODS: This retrospective cohort study included 670 patients who underwent open PD from January 2003 to December 2017. The patients were classified into ERAS (n = 352) and non-ERAS (n = 318) groups. Patients' characteristics, perioperative outcomes, and readmission rates were compared. RESULTS: There were no significant differences in the postoperative complication rates between the groups. The mean postoperative hospital stay was significantly shorter in the ERAS group (24.5 vs. 18.0 days, P < 0.001), but the 90-day readmission rate was similar in the 2 groups (9.1% vs. 8.5%, P = 0.785). Complications associated with pancreatic fistula (42.4%) were the most common cause for readmission. In the multivariate analysis, diabetes mellitus (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.05-3.24; P = 0.034), preoperative non-jaundice (OR, 0.45; 95% CI, 0.25-0.82; P = 0.009) and severe postoperative complications (OR, 4.12; 95% CI, 2.34-7.26; P < 0.001) were identified as risk factors for readmission. CONCLUSION: The results confirmed that the ERAS program for PD was beneficial in reducing postoperative stay without increasing readmission risks. To decrease readmission rates, prudent discharge planning and medical support should be considered in patients who experience severe complications.

Generation and manipulation of isotropic droplets in nematic medium using switchable dielectrophoresis.

Dielectrophoresis (DEP) in a medium with anisotropic dielectric susceptibility is very different from typical DEP in an isotropic medium: The direction of particle actuation can be switched depending on the direction of the susceptibility tensor of the medium. However, the understanding of switchable DEP (SDEP) in an anisotropic medium is still in its infant stage. Here, we investigate SDEP using heat-generated isotropic droplets in a nematic liquid crystal (LC) medium. We demonstrate that the location of the generation of isotropic droplets can be partially controlled by controlling the temperature gradient within the LC cell using dielectric loss. The SDEP actuation of isotropic droplets is also highly dependent on the location of the isotropic droplets. Using this method, we fabricated different array patterns of isotropic and nematic phase separations under different applied signals.

A self-assembled nanoparticle cluster array fabricated using nematic-isotropic phase separation on a functionalized surface.

The manipulation of a large number of nanoparticles (NPs) is an interesting but challenging task. Here, we demonstrate a new method to fabricate an NP cluster array, in which the shape and size of each NP cluster can be controlled. The method involves the use of the solubility contrast of NPs in the isotropic and nematic liquid crystal (LC) media, and the isotropic-preference difference depending on the types of the surfaces. The former mechanism is used to trap NPs within the isotropic domain, the size of which is simply manipulated by adjusting temperature. The latter mechanism is used to control the location of isotropic pockets in the continuous nematic phase. By controlling the volume and location of the isotropic pocket, one can simply create various types of NP cluster arrays. This method does not involve the use of any external field, and may be applicable to other types of NPs, including ferroelectric or ferromagnetic materials, thereby expanding its applicability.

Switchable dielectrophoresis of defect-free droplets in an anisotropic liquid crystal medium.

Dielectrophoresis (DEP) is widely used in nanoscience and biology to control small particles but its applicability is significantly limited by its one-way impetus characteristics along the square field gradient (∇E2) direction, that is, DEP force, FDEP ∼ ∇E2. Here, switchable DEP (SDEP) using the anisotropic property of a nematic medium is demonstrated; FDEP does not need to be parallel to ∇E2 but is arbitrarily changeable depending on the permittivity tensor orientation of the medium. To effectively demonstrate the SDEP phenomenon, isotropic droplets with infinitesimal surface anchoring in a nematic medium are introduced, in which topological defects of the nematic medium around dispersed objects are effectively eliminated. The experimental behaviours are well explained by theoretical and simulation results. To emphasize the applicability of SDEP, switchable arrays of isotropic droplets and an isotropic pocket carrier system containing micro-particles are demonstrated. The results reveal a new dimension of DEP and provide a novel approach for manipulating nano- or micro-materials in colloids.

Draft genome sequence of Kocuria rhizophila P7-4.

We report the draft genome sequence of Kocuria rhizophila P7-4, which was isolated from the intestine of Siganus doliatus caught in the Pacific Ocean. The 2.83-Mb genome sequence consists of 75 large contigs (>100 bp in size) and contains 2,462 predicted protein-coding genes.

Genome sequence of Acinetobacter sp. strain P8-3-8, isolated from Fistularia commersonii in Vietnam.

Acinetobacter sp. strain P8-3-8 is an aerobic, Gram-negative marine bacterium isolated from the intestine of the bluespotted cornetfish (Fistularia commersonii). Here, we present the draft genome sequence of Acinetobacter sp. P8-3-8 (3,905,565 bp, with a G+C content of 37.6%) containing 3,621 putative coding sequences. The genome data reveal a high density of genes encoding transcriptional regulators involved in anaerobic respiration.

Sequence and expression analysis of extracellular signal-regulated kinase 1 from flounder (Paralichthys olivaceous).

Extracellular signal-regulated kinases (ERKs) are a subgroup of mitogen-activated protein kinases (MAPK) that function as important intermediates in signal transduction pathways initiated by several types of cell surface receptors. We cloned a transcript of ERK1 from a cDNA library of flounder leukocytes stimulated with bacterial lipopolysaccharide and hemagglutinin lectin. Flounder ERK1 consists of 1502 nucleotides and encodes a polypeptide of 393 amino acids. Flounder ERK1 showed 90 and 89% amino acid sequence identity to ERK1 of carp and zebrafish, respectively, and over 85% to that of mammals. Multiple bands were detected by Southern blot analysis of flounder genomic DNA after digestion with various restriction enzymes, implying the presence of additional MAPK genes in flounder. Real-time PCR revealed the ubiquitous expression of flounder MAPK in all tissues with high levels of transcription in brain, gill, and fin, but not in muscle or skin. Flounder MAPK was successfully expressed in mammalian COS1 cells and phosphorylated myelin basic protein (MBP) substrate when the cells were stimulated with PMA or EGF, indicating that flounder MAPK is functional in animal cells.