Novel Characterization of Constipation Phenotypes in ICR Mice Orally Administrated with Polystyrene Microplastics.

Indirect evidence has determined the possibility that microplastics (MP) induce constipation, although direct scientific proof for constipation induction in animals remains unclear. To investigate whether oral administration of polystyrene (PS)-MP causes constipation, an alteration in the constipation parameters and mechanisms was analyzed in ICR mice, treated with 0.5 µm PS-MP for 2 weeks. Significant alterations in water consumption, stool weight, stool water contents, and stool morphology were detected in MP treated ICR mice, as compared to Vehicle treated group. Also, the gastrointestinal (GI) motility and intestinal length were decreased, while the histopathological structure and cytological structure of the mid colon were remarkably altered in treated mice. Mice exposed to MP also showed a significant decrease in the GI hormone concentration, muscarinic acetylcholine receptors (mAChRs) expression, and their downstream signaling pathway. Subsequent to MP treatment, concentrations of chloride ion and expressions of its channel (CFTR and CIC-2) were decreased, whereas expressions of aquaporin (AQP)3 and 8 for water transportation were downregulated by activation of the mitogen-activated protein kinase (MAPK)/nuclear factor (NF)-κB signaling pathway. These results are the first to suggest that oral administration of PS-MP induces chronic constipation through the dysregulation of GI motility, mucin secretion, and chloride ion and water transportation in the mid colon.

Effect of polydiacetylene-based nanosomes on cell viability and endocytosis.

Polydiacetylene-based nanoparticles have been developed as nanocarriers for various bio-applications. However, how nanocarriers enter the cell environment and affect cell viability has not yet been considerably explored. In this study, polydiacetylene-based nanoliposomes (nanosomes) were electrostatically complexed with rhodamine fluorophores. Based on real-time cell imaging and cell viability assessment, the most highly polymerized nanosomes were found to be less toxic to cells. Moreover, it was revealed that the rhodamine/polydiacetylene nanosome complex dissociates at cell environment, the polydiacetylene nanosome penetrates into cells, as suggested by the fluorescence observed in confocal microscopy images.

Metal Ion-Mediated Interliposomal Aggregation of Polydiacetylene Liposomes Incorporating a Phenolic Lipid.

Intercolloidal behaviors mediated by metal-ligand coordination have rarely been studied. In this work, such intercolloidal behaviors were demonstrated visibly using blue-colored polydiacetylene liposomes containing a phenolic lipid that acts as a binding ligand toward metal ions. The optimized liposomes were 150-200 nm in diameter and stable in aqueous solution. In incubation tests with various neocortical metal ions, iron(III) ions produced the most obvious colloidal aggregation of the liposomes. As the pH of the incubation medium was increased from acid to basic, stronger aggregation and increased precipitation behavior were observed. The phenolic lipid is believed to contribute to the interliposomal bridging interaction, and the pH dependence of the complexation between iron(III) and the phenolic lipid inserted in the liposomes were verified.

Underwater contact adhesion and microarchitecture in polyelectrolyte complexes actuated by solvent exchange.

Polyelectrolyte complexation is critical to the formation and properties of many biological and polymeric materials, and is typically initiated by aqueous mixing followed by fluid-fluid phase separation, such as coacervation. Yet little to nothing is known about how coacervates evolve into intricate solid microarchitectures. Inspired by the chemical features of the cement proteins of the sandcastle worm, here we report a versatile and strong wet-contact microporous adhesive resulting from polyelectrolyte complexation triggered by solvent exchange. After premixing a catechol-functionalized weak polyanion with a polycation in dimethyl sulphoxide (DMSO), the solution was applied underwater to various substrates whereupon electrostatic complexation, phase inversion, and rapid setting were simultaneously actuated by water-DMSO solvent exchange. Spatial and temporal coordination of complexation, inversion and setting fostered rapid (∼25 s) and robust underwater contact adhesion (Wad ≥ 2 J m(-2)) of complexed catecholic polyelectrolytes to all tested surfaces including plastics, glasses, metals and biological materials.

Microphase Behavior and Enhanced Wet-Cohesion of Synthetic Copolyampholytes Inspired by a Mussel Foot Protein.

Numerous attempts have been made to translate mussel adhesion to diverse synthetic platforms. However, the translation remains largely limited to the Dopa (3,4-dihydroxyphenylalanine) or catechol functionality, which continues to raise concerns about Dopa's inherent susceptibility to oxidation. Mussels have evolved adaptations to stabilize Dopa against oxidation. For example, in mussel foot protein 3 slow (mfp-3s, one of two electrophoretically distinct interfacial adhesive proteins in mussel plaques), the high proportion of hydrophobic amino acid residues in the flanking sequence around Dopa increases Dopa's oxidation potential. In this study, copolyampholytes, which combine the catechol functionality with amphiphilic and ionic features of mfp-3s, were synthesized and formulated as coacervates for adhesive deposition on surfaces. The ratio of hydrophilic/hydrophobic as well as cationic/anionic units was varied in order to enhance coacervate formation and wet adhesion properties. Aqueous solutions of two of the four mfp-3s-inspired copolymers showed coacervate-like spherical microdroplets (ϕ ≈ 1-5 µm at pH ∼4 (salt concentration ∼15 mM). The mfp-3s-mimetic copolymer was stable to oxidation, formed coacervates that spread evenly over mica, and strongly bonded to mica surfaces (pull-off strength: ∼17.0 mJ/m(2)). Increasing pH to 7 after coacervate deposition at pH 4 doubled the bonding strength to ∼32.9 mJ/m(2) without oxidative cross-linking and is about 9 times higher than native mfp-3s cohesion. This study expands the scope of translating mussel adhesion from simple Dopa-functionalization to mimicking the context of the local environment around Dopa.

Polydiacetylene liposome microarray toward influenza a virus detection: effect of target size on turn-on signaling.

Target size effect on the sensory signaling intensity of polydiacetylene (PDA) liposome microarrays was systematically investigated. Influenza A virus M1 peptide and M1 antibody were selected as a probe-target pair. While red fluorescence from the PDA liposome microarrays was observed when the larger M1 antibody was used as a target, when the same M1 antibody was used as a probe to detect the smaller M1 peptide sensory signal did not appear. The results reveal that the intensity of the PDA sensory signal is mainly related to the steric repulsion between probe-target complexes not the strength of the probe-target binding force. Based on this finding, we devised a PDA sensory system that directly detects influenza A whole virus as a larger target, and confirmed the target size effect on the signaling efficiency of PDA.

Design of polydiacetylene-phospholipid supramolecules for enhanced stability and sensitivity.

We present polydiacetylene (PDA) liposome assemblies with various phospholipids that have different headgroup charges and phase transition temperatures (T(m)). 10,12-Pentacosadiynoic acid (PCDA)-epoxy was used as a base PDA monomer and the insertion of highly charged phospholipids resulted in notable changes in the size of liposome and reduction of the aggregation of PDA liposome. Among the various phospholipids, the phospholipid with a moderate T(m) demonstrated enhanced stability and sensitivity, as measured by the size and zeta potential over storage time, thermochoromic response, and transmission electron microscopy images. By combining these results, we were able to detect immunologically an antibody of bovine viral diarrhea virus over a wide dynamic range of 0.001 to 100 µg/mL.

Promoting Effects of Titanium Implants Coated with Dipterocarpus tuberculatus Extract on Osseointegration.

Titanium (Ti) is the most commonly used biomaterial for dental implants. When inserting Ti implants into jawbones, the main issue is the lack of strong bonding between the Ti implant and the host bone (osseointegration). Inspired by the outstanding adhesion performance of natural phenolic compounds on metal substrates and promoting effect for cell adhesion, we coated a natural plant extract, Dipterocarpus tuberculatus (MED), on Ti implants. We tested three groups of Ti plates and screw-shaped fixtures: nontreated Ti as commercially produced, ozone-treated Ti as commonly used surface modification for dental implants, and MED-coated Ti. Interestingly, the MED coating on the Ti plate preserved the surface wetting property for 20 days, whereas the hydrophilic wetting of ozone-treated Ti was readily transformed to hydrophobic within a day. Computerized tomography and histopathological analysis revealed that MED coating enhanced new bone tissue formation and regeneration. The gene expression level of integrin as a bone cell adhesion receptor and its downstream key regulators was significantly increased than that of ozone-treated Ti. Therefore, we suggest considering MED-mediated cell signaling pathways in screening natural products for cell adhesion and osseointegration, and MED as a suitable coating agent for improving Ti implantation.

In vivo impact assessment of orally administered polystyrene nanoplastics: biodistribution, toxicity, and inflammatory response in mice.

To assess the in vivo impact of nanoplastics (NP) and coagulation-based purified NP (PurNP), this study analyzed for alterations in the biodistribution, toxicity and inflammatory response in ICR mice exposed to three different doses of NP (5, 25, and 50 mg/kg) and PurNP for 2 weeks. Except water consumption, which was dose-dependently and significantly increased in all NP-treated groups, most factors assessed for feeding behaviors and excretions remained constant, without any significant change. Orally administered NP was detected in the intestine, kidneys, and liver at all concentrations, although the accumulation was higher in the intestine than in the kidneys and liver. No significant alterations were detected in the levels of serum biochemical markers and histopathological structures. However, compared to the vehicle group, expressions of the inflammatory response proteins (iNOS and COX-2) and mRNA levels of the inflammatory cytokines were remarkably increased in the liver, kidneys, and intestine of NP-treated mice. A similar increase was detected in the oxidative stress responses, including ROS concentration, SOD activity, and Nrf2 expression. Furthermore, similar inflammatory responses were observed in the PurNP-treated group, as compared to the vehicle-treated group. The results presented in this study provide the first strong evidence that oral administration of NP for 2 weeks results in high accumulation in the liver, kidneys, and intestine of ICR mice, and induces severe inflammatory and oxidative stress responses. These results additionally confirm the efficacy of water purification using the tannic acid-mediated coagulation removal technique.

Polydiacetylene Liposome Microarray toward Facile Measurement of Platelet Activation in Whole Blood.

The necessity of a simple measurement of platelet activation has been increasing in clinical medicine to regulate the proper dose of the antiplatelet drugs for patients having clinical outcomes in acute situations such as angina pectoris, stroke, or peripheral vascular disease or procedures involving angioplasty or coronary thrombolysis. We developed a self-signaling polydiacetylene (PDA) liposome microarray to detect activated platelets from whole blood samples in a single step. A specific antibody, 9F9 antibody, to platelet-bound fibrinogen was selected and conjugated to the PDA liposome microarray to quantify the fibrinogen-bound platelets. The developed PDA liposome-9F9 microarray generated an intense fluorescence signal when activated platelets in whole blood were introduced and also successfully distinguished the reduced platelet activation in the presence of Tirofiban, a model antiplatelet drug. The results of this single-step benchtop assay incorporates simple, sensitive, and rapid attributes that can detect the extent of platelet activation prior to needed clinical procedures.

Enhancement of cellular binding efficiency and cytotoxicity using polyethylene glycol base triblock copolymeric nanoparticles for targeted drug delivery.

Folate (FA) conjugated tri-block copolymers were prepared by bioconjugation of poly epsilon-caprolactonediol and various molecular weights of diamine polyethylene glycol. The synthetic tri-block copolymers were characterized by 1H-NMR. Three types of nanoparticles were prepared by nanoprecipitation. Their size and morphology were verified by laser scattering and transmission electron microscopy, respectively. The colloidal stability of the nanoparticles was evaluated by turbidity test. The anticancer drug doxorubicin (DOX) was encapsulated in the nanoparticles during preparation. Drug loading amounts and release behavior from prepared nanoparticles were investigated. Fluorescent-activated cell sorting analysis and epi-fluorescencic microscopic imaging of prepared nanoparticles exhibited good cellular uptake against target cells. FA receptor expressed OVCAR3 cells that showed higher mean fluorescence intensity than FA receptor defect A549 cells at specific polyethylene glycol chain lengths. The cell cytotoxicity of prepared nanoparticles was evaluated for receptor mediated drug delivery.

Highly sensitive turn-on biosensors by regulating fluorescent dye assembly on liposome surfaces.

We developed a new self-signaling sensory system built on phospholipid liposomes having H-aggregated R6G dyes on their surface. Selective molecular recognition of a target by the phospholipid displaces R6G from the liposome surface to turn on fluorescence signal. Selective and sensitive detection of neomycin down to 2.3 nM is demonstrated.

Janus-compartmental alginate microbeads having polydiacetylene liposomes and magnetic nanoparticles for visual lead(II) detection.

Janus-compartmental alginate microbeads having two divided phases of sensory polydiacetylene (PDA) liposomes and magnetic nanoparticles were fabricated for facile sensory applications. The sensory liposomes are composed of PDA for label-free signal generation and 1,2-dipalmitoyl-sn-glycero-3-galloyl (DPGG) lipids whose galloyl headgroup has specific interactions with lead(II). The second phase having magnetic nanoparticles is designed for convenient handling of the microbeads, such as washing, solvent exchange, stirring, and detection, by applying magnetic field. Selective and convenient colorimetric detection of lead(II) and efficient removal of lead(II) by alginate matrix at the same time are demonstrated.

Biomimetic detection of aminoglycosidic antibiotics using polydiacetylene-phospholipids supramolecules.

We rationally designed highly sensitive and selective polydiacetylene (PDA)-phospholipids liposomes for the facile detection of aminoglycosidic antibiotics. The detecting mechanism mimics the cellular membrane interactions between neomycin and phosphatidylinositol-4,5-bisphosphate (PIP(2)) phospholipids. The developed PDA-PIP(2) sensory system showed a detection limit of 61 ppb for neomycin and was very specific to aminoglycosidic antibodies only.