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•pH-/thermo-responsive hydrogels were prepared using PAA, CsNb, and bisTz-PNIPAM.•Porous structure formed by Tz-Nb reaction greatly increased the drug loading content.•Hydrogels ...released a much higher amount of drug at pH 7.4 than at pH 2.2.•The drug release from hydrogels was enhanced at 37 °C via “shrinkage” of PNIPAM.
A dual pH-/thermo-responsive hydrogel was designed based on a polyelectrolyte complex of polyacrylic acid (PAA) and norbornene-functionalized chitosan (CsNb), which was synergized with chemical crosslinking using bistetrazine-poly(N-isopropyl acrylamide) (bisTz-PNIPAM). The thermo-responsive polymeric crosslinker, bisTz-PNIPAM, was synthesized via reversible addition–fragmentation transfer polymerization of NIPAM. FTIR, XRD, rheological and morphological analyses demonstrated the successful formation of the polyelectrolyte network. The highly porous structure generated through the in-situ “click” reaction between Tz and Nb resulted in a higher drug loading (29.35 %). The hydrogel (COOH/NH2 mole ratio of 3:1) exhibited limited drug release (8.5 %) of 5-ASA at a pH of 2.2, but it provided an almost complete release (92 %) at pH 7.4 and 37 °C within 48 h due to the pH responsiveness of PAA, hydrogel porosity, and shrinkage behavior of PNIPAM. The hydrogels were biodegradable and non-toxic against human fibroblast cells, suggesting their considerable potential for a colon-targeted drug delivery system.
Huntington's disease (HD), an inherited neurodegenerative disorder, is caused by an expansion of cytosine-adenine-guanine repeats in the huntingtin gene. The aggregation of mutant huntingtin (mtHTT) ...and striatal cell loss are representative features to cause uncontrolled movement and cognitive defect in HD. However, underlying mechanism of mtHTT aggregation and cell toxicity remains still elusive. Here, to find new genes modulating mtHTT aggregation, we performed cell-based functional screening using the cDNA expression library and isolated IRE1 gene, one of endoplasmic reticulum (ER) stress sensors. Ectopic expression of IRE1 led to its self-activation and accumulated detergent-resistant mtHTT aggregates. Treatment of neuronal cells with ER stress insults, tunicamycin and thapsigargin, increased mtHTT aggregation via IRE1 activation. The kinase activity of IRE1, but not the endoribonuclease activity, was necessary to stimulate mtHTT aggregation and increased death of neuronal cells, including SH-SY5Y and STHdhQ111/111 huntingtin knock-in striatal cells. Interestingly, ER stress impaired autophagy flux via IRE1-TRAF2 pathway, thus enhancing cellular accumulation of mtHTT. Atg5 deficiency in M5-7 cells increased mtHTT aggregation but blocked ER stress-induced mtHTT aggregation. Further, ER stress markers including p-IRE1 and autophagy markers such as p62 were up-regulated exclusively in the striatal tissues of HD mouse models and in HD patients. Moreover, down-regulation of IRE1 expression rescues the rough-eye phenotype by mtHTT in a HD fly model. These results suggest that IRE1 plays an essential role in ER stress-mediated aggregation of mtHTT via the inhibition of autophagy flux and thus neuronal toxicity of mtHTT aggregates in HD.
One of the most promising strategies for the controlled release of therapeutic molecules is stimuli-responsive and biodegradable hydrogels developed from natural polymers. However, current strategies ...to development stimuli-responsive hydrogels lack precise control over drug release profile and use cytotoxic materials during preparation. To address these issues, multi-stimuli responsive hydrogels derived from hyaluronic acid and diselenide based cross-linker were developed for the controlled release of doxorubicin (DOX). Hydrogels were rapidly formed via an inverse electron demand Diels–Alder click chemistry and encapsulated DOX/indocyanine green (ICG) in their porous networks. The hydrogels showed a rapid release of DOX in acidic (pH 5), reducing (10 mmol DTT), and oxidizing medium (0.5% H2O2), and after NIR irradiation. The in vitro experiments demonstrated that hydrogels were highly cytocompatible and the DOX-loaded hydrogels induced similar anti-tumor effect as compared to that of the free-DOX. Furthermore, DOX + ICG loaded hydrogels increased the antitumor efficacy of DOX after NIR irradiation.
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A novel physically and chemically double-crosslinked hydrogel derived from chitosan oligosaccharide/alginate (COS/Alg) was developed by using norbornene (Nb)-tetrazine (Tz) click reaction for ...ketoprofen delivery. The properties of the hydrogel were evaluated by rheological, FTIR, TGA, XRD, SEM, swelling and drug release studies. The Nb-Tz chemical cross-linking facilitated outstanding hydrophobic drug loading (44% wt/wt of ketoprofen) and sustained release through a hydrophobic interaction mechanism between the drug and the used polysaccharides. The COS/Alg electrostatics network (10/10 of NH2/COOH molar ratio) generated the pH responsiveness, suppressing the release in simulated gastric fluid (below 10% for 2 h) and enhancing the release in simulated intestinal fluids (up to 84% for 24 h). The prepared hydrogel was non-toxic to human HEK-293 cells (95% cell viability). This work opens up a potential approach for preparing hydrophilic hydrogels from natural polysaccharides that can be used in the delivery of hydrophobic drugs.
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The ability to image pressure distribution over complex three-dimensional surfaces would significantly augment the potential applications of electronic skin. However, existing methods show poor ...spatial and temporal fidelity due to their limited pixel density, low sensitivity, or low conformability. Here, we report an ultraflexible and transparent electroluminescent skin that autonomously displays super-resolution images of pressure distribution in real time. The device comprises a transparent pressure-sensing film with a solution-processable cellulose/nanowire nanohybrid network featuring ultrahigh sensor sensitivity (>5000 kPa
) and a fast response time (<1 ms), and a quantum dot-based electroluminescent film. The two ultrathin films conform to each contact object and transduce spatial pressure into conductivity distribution in a continuous domain, resulting in super-resolution (>1000 dpi) pressure imaging without the need for pixel structures. Our approach provides a new framework for visualizing accurate stimulus distribution with potential applications in skin prosthesis, robotics, and advanced human-machine interfaces.
We investigated the spatial variability of macrofaunal and meiofaunal assemblages in intertidal flats on the southern coast of Korea. Abiotic and biotic samples were collected at five stations. The ...species richness, density, and composition of the assemblages differed significantly among stations. Nematoda and Annelida were the most dominant meiofaunal and macrofaunal taxa, respectively, although taxon dominance differed among stations. Distance-based linear models showed that sediment-related variables and heavy metals were the main environmental factors determining the spatial variability of the assemblages. Macrofauna had only sediment-related variables and heavy metals as major environmental factors, but meiofauna were also influenced by other environmental factors such as sea surface temperature, dissolved oxygen-related variables, and salinity. This study can provide basic ecological data for understanding the spatial distribution of macro-meiofaunal assemblages and aid in the development of marine environmental management strategies on the western south coast of Korea.
•Grain size and organic matter determined spatial variability of benthic assemblages.•Meiofauna more sensitive to site-specific environmental variables than macrofauna.•Macro-meiofauna have been affected by sediment properties and heavy metals.
Risk screening tools are being increasingly used to identify the potential invasiveness and associated risks of non-native species. In this study, the Aquatic Species Invasiveness Screening Kit was ...used to evaluate the invasiveness risks of extant and horizon non-native marine fish species for the coastal waters of South Korea. In total, 57 marine fish species were screened and the threshold scores for the Basic Risk Assessment (BRA) and the BRA + Climate Change Assessment (BRA+CCA) (5.5 and 1.5, respectively) reliably distinguished those species carrying a high risk of invasiveness from those carrying a low to medium risk. For both the BRA and BRA+CCA, common lionfish Pterois miles was the highest-scoring species, followed by white perch Morone americana, red drum Sciaenops ocellatus, marbled spinefoot Siganus rivulatus and redcoat Sargocentron rubrum. The outcomes of this study will contribute to the management of non-native marine fish species for the conservation of the native ecosystems in the coastal waters of South Korea.
•Out of 57 marine fish species assessed, 18 were classified as high risk.•45 species increased invasiveness risk by climate change assessment.•Climate change assessment resulted an increase in all very high risk species.•Standard errors indicated overall similarity in confidence levels and factors.
The spawning, development, and early life cycle of three species of marine nematodes in Mallipo, Korea, were studied. With regard to
Bathylaimus
sp., the number of spawned eggs ranged from four to ...ten, with an average of seven. The mean hatching time was 99.5 h, while body size was 320–400 μm immediately after hatching and 680–800 μm 1 week after hatching. Twenty-eight days after hatching,
Bathylaimus
sp. had grown to 1900–2200 μm, which is similar to its adult size and female
Bathylaimus
sp. developed vulva, and male
Bathylaimus
sp. developed a spicule. The adult body size of
Oncholaimus
sp., a scavenger, was 3300–3700 μm, and the number of spawned eggs was 4 to 7 (average 5.2). Spawning to hatching took 72–96 h (average 81 h) and the mean hatching rate was 96.1%. The hatched juveniles grew to 1100–1250 μm 4 days after hatching and 2100–2400 μm 15 days after hatching, which was about 65% of the adult body size. The adult body size of
Oncholaimellus
sp., another scavenger, was 850–1100 μm, and the number of spawned eggs ranged from 2 to 8 (average 5.3). Spawning to hatching took 52–72 h, with an average of 60 h, and the mean hatching rate was 90.5%. The size of the juveniles ranged from 220–300 μm immediately after hatching to 460–550 μm 5 days after hatching, which was about 50% of the adult body size.
Near-infrared (NIR) light-responsive hydrogels have emerged as a highly promising strategy for effective anticancer therapy owing to the remotely controlled release of chemotherapeutic molecules with ...minimal invasive manner. In this study, novel NIR-responsive hydrogels were developed from reactive oxygen species (ROS)-cleavable thioketal cross-linkers which possessed terminal tetrazine groups to undergo a bio-orthogonal inverse electron demand Diels Alder click reaction with norbornene modified carboxymethyl cellulose. The hydrogels were rapidly formed under physiological conditions and generated N2 gas as a by-product, which led to the formation of porous structures within the hydrogel networks. A NIR dye, indocyanine green (ICG) and chemotherapeutic doxorubicin (DOX) were co-encapsulated in the porous network of the hydrogels. Upon NIR-irradiation, the hydrogels showed spatiotemporal release of encapsulated DOX (>96 %) owing to the cleavage of thioketal bonds by interacting with ROS generated from ICG, whereas minimal release of encapsulated DOX (<25 %) was observed in the absence of NIR-light. The in vitro cytotoxicity results revealed that the hydrogels were highly cytocompatible and did not induce any toxic effect on the HEK-293 cells. In contrast, the DOX + ICG-encapsulated hydrogels enhanced the chemotherapeutic effect and effectively inhibited the proliferation of Hela cancer cells when irradiated with NIR-light.
In this study, we report a near‐infrared (NIR)‐responsive interface cross‐linked (ICL) micelles prepared by using the Diels–alder (DA) click reaction between poly(D,L‐lactide)‐b‐poly(furfuryl ...methacrylate)‐b‐poly(N‐acryloylmorpholine) (PLA‐b‐PFMA‐b‐PNAM) triblock copolymers and a diselenide cross‐linker, bis(maleimidoethyl) 3,3′‐diselanediyldipropionoate (BMEDSeDP). PLA‐b‐PFMA‐b‐PNAM was synthesized by the sequential RAFT polymerization of FMA and NAM using PLA‐macro‐chain transfer agent (PLA‐CTA) as a macro‐initiator. The DA reaction between BMEDSeDP and the furfuryl moiety in the triblock copolymer resulted in the formation of ICL micelles. The ICL micelles were analyzed by 1H NMR, FE‐SEM and DLS methods. An anticancer drug, doxorubicin (DOX) was in situ incorporated into the ICL micellar core to prepare drug loaded ICL micelles. The release of DOX from the ICL micelles was suppressed (ca. 11% in 60 h) under physiological conditions (pH 7.4), indicating that the interfacial cross‐linking greatly protected the drug release from the micelles. Interestingly, the DOX‐loaded ICL micelles showed pH and NIR‐responsive drug release profile, and the highest release was observed under NIR laser irradiation at pH 5.0. The in vitro toxicity analysis demonstrated that the ICL was not basically cytotoxic against normal HFF‐1 cells (non‐cancerous), while higher antitumor activity towards HeLa cells were exhibited by DOX‐loaded ICL micelles. The developed ICL micelles would provide a promising robust anticancer drug delivery system for the future cancer treatment.
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