Adsorbents prepared from epoxy-based porous materials of microcrystalline cellulose for excellent adsorption of anionic and cationic dyes.

It reported a porous material prepared from microcrystalline cellulose (MCC), to achieve rapid preparation of adsorbents. The porous material was characterized by several tools including 1H NMR, FTIR, XPS, and SEM. Two adsorbents were prepared and subjected to adsorption experiments. Dye adsorption experiments show that the adsorption driving is electrostatic interactions and the process is chemisorption. The maximum capacity of Microcrystalline cellulose-g-Poly (glycidyl methacrylate)-Tannins (MPT) reached 191.3 (Methylene blue), 123.7 mg g-1 (Rhodamine B), and Microcrystalline cellulose-g-Poly (glycidyl methacrylate)-Lysine (MPL) attained 425.8 (Methylene blue), 480.7 mg g-1 (Methyl orange). The results were followed the pseudo-second-order (PSO) and agreed with the Langmuir fit model. Adsorption-desorption cycling experiments further indicate that the adsorbent possesses outstanding reproducibility. At last, epoxidized bio-porous materials are positive in the preparation of dye adsorbents with critical adsorption properties.

Overcoming the structure deficiency of nanodrug coated with tannic acid shell through phenolic hydroxyl protection strategy for Alzheimer's disease combination treatment.

Tannic acid (TA) shell is of great interest for nanodrug design due to its versatile application such as antioxidant, antibacterial, anti-inflammatory. However, evidence is emerging that TA air oxidation in storage stage and unfavorable interactions of TA with electrolyte or protein in drug delivery could bring great challenge for the structure stability of nanodrug. In this study, a smart TA shell of nanomicelles was constructed through phenolic hydroxyl protection strategy, and the antioxidant capacity of nanomicelles maintain stable after 24 days storage. The phenolic hydroxyl protective tannic acid micelles (PHPTA micelles) show excellent performance for combination delivery of azoramide (Azo), dantrolene (Dan), Trazodone (Tra) in accelerated senescence (SAMP8) mice. This study may pave the way for the fabrication of nanodrugs with stable and smart TA shell for oxidative stress relevant diseases.

Combined Core Stability and Degradability of Nanomedicine via Amorphous PDLLA-Dextran Bottlebrush Copolymer for Alzheimer's Disease Combination Treatment.

Nanomedicine faces the challenges of infinite dilution, shear force, biological protein, or electrolyte competition. However, core cross-linking leads to biodegradability deficiency and brings inevitable side effects of nanomedicine on normal tissues. In order to overcome this bottleneck problem, we turn to amorphous poly(d,l)lactic acid (PDLLA)-dextran bottlebrush to emphasize the core stability of nanoparticles, and the amorphous structure offers an additional advantage of fast degradation property over the crystalline PLLA polymer. The graft density and side chain length of amorphous PDLLA together played important influence roles in controlling the architecture of nanoparticles. This effort produces structure-abundant particles, including micelles, vesicles, and large compound vesicles after self-assembly. Here, the amorphous bottlebrush PDLLA was verified to play a beneficial role in the structure stability and degradability of nanomedicines. The codelivery of the hydrophilic antioxidant of citric acid (CA), vitamin C (VC), and gallic acid (GA) via the optimum nanomedicines could effectively repair the SH-SY5Y cell damage caused by H2O2. The CA/VC/GA combination treatment repaired the neuronal function efficiently, and the cognitive abilities of senescence-accelerated mouse prone 8 (SAMP8) recovered.

Polypropylene fiber grafted calcium alginate with mesoporous silica for adsorption of Bisphenol A and Pb2.

Polypropylene grafted calcium alginate with mesoporous silica (PP-g-CaAlg@SiO2) for adsorbing Bisphenol A (BPA) and Pb2+ was prepared by calcium chloride (CaCl2) crosslinking and hydrochloric acid solution treatment. The PP-g-CaAlg@SiO2 was characterized by SEM, TEM, BET, XRD, FTIR and TG. PP-g-CaAlg@SiO2 exhibited excellent adsorption capacity for BPA and Pb2+, because the formation of reticulated nanorod structure increased its specific surface area. Subsequently, the adsorption behaviours of BPA and Pb2+, including adsorption isotherms and adsorption kinetics, were investigated. Afterward, isothermal titration calorimetry (ITC) and molecular dynamics (MD) simulation were performed to explore the adsorption mechanism. The results indicated that hydrogen bonding played the leading role in the adsorption of BPA, while the bonding of Pb2+ to carboxyl group binding sites was the focus of Pb2+ adsorption. In addition, the adsorption capacity of PP-g-CaAlg@SiO2 was stable over 10 cycles.

Prevent Drug Leakage via the Boronic Acid Glucose-Insensitive Micelle for Alzheimer's Disease Combination Treatment.

Boronic acid (BA) materials have been widely applied to glucose and oxidative stress-sensitive drug delivery for the treatment of cancer, diabetes, and Alzheimer's disease (AD). There are completely various BA-sensitive delivery conditions in different diseases. BA materials in the treatment of diabetes show better performance at a high-glucose environment than normal. In contrast, the concentration of glucose in the brain is much lower than that in the blood of AD patients. Hence, the typical glucose and oxidative stress dual-sensitive BA materials inevitably encounter drug leakage in circulation in AD. Attempts to decrease the glucose-sensitive capacity of BA materials are extremely essential for AD drug delivery. In this study, the epoxy group (electron-donating group) was introduced to increase the pKa values of BA materials by increasing the electron cloud density, and thus, the glucose-insensitive micelle (GIM) was obtained. The treatment effect and the synergism mechanism of the drug-loaded GIM micelle were studied on senescence-accelerated mouse prone 8 mice. This work provided excellent antioxidant drugs (vitamin E succinate, melatonin, and quercetin) and a glucose metabolism drug (insulin) loaded in GIM micelle for AD treatment. The discovery of the combination mechanism is enormously valuable for AD clinical research.

Ultra-stable dextran conjugated prodrug micelles for oxidative stress and glycometabolic abnormality combination treatment of Alzheimer's disease.

Sophisticated nanomedicines are continually being developed, but big obstacles remain before they finish the drug release mission. The first challenge is rupture possibility of structure when infinite dilution, competitive reaction of electrolytes and protein in blood circulation. In addition, low responsive drug release efficiency in the lesion site remains the major challenge for clinical application of nanomedicine combination treatment. In this study, we discussed the opportunities for Alzheimer's disease (AD) combination therapy based on the thermodynamically ultra-stable dextran conjugated prodrug micelles. Dextran-nateglinide conjugated prodrug micelles (NA) and dextran-vitamin E succinate conjugated prodrug micelles (VES) presented ultra-low critical micelle concentration of ~10-5 mM and high physiological stability when challenged by NaCl, sodium dodecyl sulphate (SDS), dodecyl dimethyl benzyl ammonium chloride (DDBAC) and no rupture of structure happened. The NA/insulin polymer-drug conjugate micelles (NA/INS PDC) and VES/insulin polymer-drug conjugate micelles (VES/INS PDC) efficiently cleaved by reactive oxygen species (ROS), leading to over 80% release of the encapsulated and conjugated drugs. The combination of nateglinide and insulin, vitamin E succinate and insulin improved the glucose metabolism, reduced oxidative stress, improved the mitochondrial function and recovered the cognitive capacity of mice. This work demonstrated a paradigm for specific and high efficacy AD combination therapy.

Hydrophilic hindering and hydrophobic growing: a vesicle glycometabolism multi-drug combination therapeutic against Alzheimer's disease.

Advanced drug vehicle exploitation and the sophisticated synergy mechanism revelation are two great difficulties in combination therapy. Compared with most readily available polymer micelles, some undiscovered complex chemical design principles limit the expanding research of polymer vesicles. Here, polycaprolactone (PCL)-g-Dextran vesicle that dextran brush steric hindrance guide PCL lamellae-aligned growth was synthesized. The effect of the glycometabolism multi-drug vesicle combination treatment and synergism mechanism were investigated on senescence-accelerated mouse prone 8 (SAMP8) mice. The main insulin sensitizer drug could improve the memory ability of mice to a small extent, and the main insulin secretion promoter drug had little beneficial effect. Moreover, the triple anti-insulin resistant drugs of insulin (INS), repaglinide (REP) and metformin hydrochloride (MET) activated the glycometabolism-related bio-signals, and the energy cycle was normalized successfully. The insulin intracellular uptake and utilization efficiency could be the reason for the gap. The upregulation of the brain-derived neurotrophic factor (BDNF) protein confirmed that the crosstalk between the mitochondria and synapse contributes to the nerve repair. This study provided an excellent drug combination vesicle to treat Alzheimer's disease (AD). The discovery of the combination mechanism leads to an improvement in the AD clinical treatment.

Hydrophilic polymer driven crystallization self-assembly: an inflammatory multi-drug combination nanosystem against Alzheimer's disease.

The hydrophobic polymer driven crystallization of self-assembled micelles is usually sufficient for their purposes in materials chemistry studies. However, with the state of smart drug delivery research, micelles alone are not enough. The principles of the self assembly driven by hydrophilic dextran brushes together with charged poly(3-acrylamidophenyl boronic acid) (PPBA) are uncovered in this study. A series of poly(ε-caprolactone)-block-poly(3-acrylamidophenyl boronic acid)-dextran (PCL-b-PPBA-Dex) micelles and vesicles are investigated as potential Alzheimer's disease (AD) treatments. Three inflammatory microenvironment responsive micelles, including celecoxib drug-loaded micelles (CEL), ibuprofen drug-loaded micelles (IBU) and telmisartan drug-loaded micelles (TEL), are developed. In vivo, CEL/IBU (mixture of CEL and IBU) and CEL/TEL (mixture of CEL and TEL) suppress the activation of glia and reduce the levels of inflammatory mediators through eliminating cyclooxygenase 2 (COX-2) signals. The CEL/TEL combination nanosystem is better at correcting neuroinflammation and improving the spatial memory ability of a senescence-accelerated mouse prone 8 model (SAMP8). We consider that the inflammation responsive combination nanosystem provides a new potential treatment for AD clinical patients.

Legumain-induced intracerebrally crosslinked vesicles for suppressing efflux transport of Alzheimer's disease multi-drug nanosystem.

Brain barrier is both a protective permeability hurdle and a limitation site where therapeutic agents are excluded to enter the target region. Designing drug vehicle to overcome this notorious barrier bottle is challenging. Herein, we construct a stimuli-responsive self-assembled nanovesicle that delivers water-soluble drugs to prevent the efflux transport of brain barriers by responding to the endogenously occurring signals in Alzheimer's disease (AD) brain microenvironment. Once stimuli-responsive vesicles are accumulated in intracerebrally, the intrinsically occurring legumain endopeptidase cleaves the Ac-Ala-Ala-Asn-Cys-Asp (AK) short peptide on the drug vesicles to expose the 1,2 thiol amino group to cyclize with the cyano groups on 2-cyano-6-aminobenzothiazole (CABT) of the chaperone vesicles, thus triggering the formation of cross-linked micrometre-scale vesicles. Such a structural alteration completely prevents further brain barriers efflux. The superior neuroprotective capacity of cross-linked vesicles is validated in senescence accelerated mouse prone 8 (SAMP8). This smart multi-drug delivery vesicle is promising to serve as a powerful system for AD treatment and can be adapted for the therapy of other central nervous system (CNS) disorders.

Increased cross-linking micelle retention in the brain of Alzheimer's disease mice by elevated asparagine endopeptidase protease responsive aggregation.

Current forms of medication for Alzheimer's disease (AD) provide a symptomatic benefit limited to those with early onset, but there is no single drug available for later stage patients. Given the recent failures of AD drugs in clinical trials, an intensive treatment strategy based on drug combination that is approved is attractive. At present, the greatest difficulty lies in the low accumulation of drugs in the brain. All hydrophilic drugs are limited by the physical and biochemical barriers within the blood-brain barrier and lipophilic drugs are often transported back into the blood by efflux pumps located in the blood-brain barrier. Here, we select elevated asparagine endopeptidase (AEP) as a target to trigger in situ cross-linking of small sized particles to form large sized drug clusters to block the efflux of the brain. Subsequently, responsive cross-linking micelles (RCMs) loaded with the acetylcholinesterase inhibitor, donepezil (DON), the microtubule therapeutic agent, Paclitaxel (PTX), and the glucose metabolism disorder regulator, insulin (INS) are investigated, with a focus on high levels of drug accumulation in the brain in AD. These smart multi-drug delivery RCMs provide a powerful system for AD treatment and can be adapted for other central nervous system (CNS) disorders.

Economic Sulfur Conversion to Functional Polythioamides through Catalyst-Free Multicomponent Polymerizations of Sulfur, Acids, and Amines.

Sulfur utilization is a global concern because of its abundant nature sources and the safety or environmental problems caused by its burning or oxidation during storage, while sulfur-containing polymers are popular materials in virtue of their fascinating properties such as metal coordination ability, high refractive indices, and semiconducting property. The synthesis of sulfur-containing polymers is challenging, especially directly from elemental sulfur. Herein, catalyst-free and scalable multicomponent polymerizations (MCPs) of all commercially available elemental sulfur, dicarboxylic acids, and diamines were reported to facilely construct 12 polythioamides with diverse and well-defined structures, high molecular weights (Mw's up to 86 200 g/mol), and excellent yields (up to 99%) from elemental sulfur. Besides commonly used aliphatic diamines, aromatic diamine monomers are also applicable to these multicomponent polymerizations, affording polythioamides with unique rigid structures and improved functionality as compared to those of the previously reported polythioamides. These polythioamides can be applied in gold recovery, which could extract a trace amount of Au3+ from practical acidic leaching solution of discarded electronic waste selectively, rapidly (1 min), sensitively (10 ppb), and efficiently (>99.99%) with high extraction capacity up to 0.60 g· Au3+/g to directly afford high-purity elemental gold after pyrolysis. The MCPs could make use of both abundantly existing sulfur waste and trace amounts of precious gold residue in electronic wastes, demonstrating their great potential in resource utilization.

The photodegradation of methylene blue in water with PVDF/GO/ZnO composite membrane.

The immobilization of photo-catalyst can effectively avoid the difficulty in recovery of the nano-catalysts after photo-degradation. In this work, PVDF/GO/ZnO composite membranes with photocatalytic performance for organic dyes were prepared by using zinc oxide (ZnO) as photo-catalyst, graphene (GO) as dispersant and poly (vinylidene fluoride) (PVDF) membrane as carrier. The effect ZnO and GO on the structure, surface composition and photocatalytic activity of PVDF/GO/ZnO composite membranes were investigated. Owing to the strong hydrophilicity of the carboxyl group, the addition of GO enhanced the dispersibility of ZnO in PVDF membranes, which was proved by SEM results. Under Xenon irradiation (300 W), the photocatalytic degradation rate of PVDF/GO/ZnO composite membranes for methylene blue (MB) could reach 86.84%. Furthermore, the photocatalytic efficiency of the composites membrane for MB was evaluated with different initial concentrations of MB, pH value of the solution, and electron trapping agent-H2O2 content. And the radical trapping experiments with different active radical scavengers showed that the oxidizing species (O2-) plays an important role in the decolorization process of MB. In summary, this work provides an efficient method to improve the photodegradability of PVDF/GO/ZnO composite membranes and has great potential in the field of water purification.

Polydopamine/cysteine surface modified hemocompatible poly(vinylidene fluoride) hollow fiber membranes for hemodialysis.

Membrane surface design is significant for the development and application of synthetic polymer hemodialysis membranes. In this study, the influence of zwitterionic cysteine on poly(vinylidene fluoride) (PVDF) hollow fiber membrane was investigated. The polydopamine layer was formed through dopamine self-polymerization on PVDF membrane surface, and then cysteine was covalent grafted onto the layer to improve the anti-biofouling property and hemocompatibility. The elementary composition of membrane surfaces was characterized by X-ray photoelectron spectroscopy. The influence of polydopamine and cysteine on modified membrane surface morphologies was studied by field emission scanning electron microscopy. The modified PVDF membranes were confirmed to have excellent hydrophilicity, stable mechanical properties and good hemocompatibility (dynamic and static anti-protein adsorption, hemolysis ratio, plasma coagulation). And these properties were increased with the incorporation of polydopamine and cysteine. The optimized modified membranes exhibited high pure water flux (∼ 195.5 L/m2 h at 0.1 MPa) and selectivity (clearance ratio of urea and lysozyme was 75.1 and 55.4%, and rejection rate of bovine serum albumin was 98.8%). This work provides a surface modification method of PVDF hollow fiber membranes and suggests a potential application of PVDF membranes in hemodialysis field. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2869-2877, 2018.

Preparation and properties of CA/ATP-g-CDs gel fibers for simultaneous detection and adsorption of methylene blue.

To detect and adsorb methylene blue (MB) from wastewater simultaneously, a solid fluorescent and absorbent material was designed by immobilizing attapulgite (ATP) on calcium alginate (CA) and reacting with carbon dots (CDs) which were modified by the activation of γ-(2,3-epoxypropoxy) propyltrimethoxysilane (KH-560), then the CA/ATP-g-CDs gel fibers were prepared. The problem of CDs easily falling out of materials was solved. The structures of the gel fibers were characterized by field emission scanning electron microscopy (FE-SEM), specific surface area (BET) and X-ray photoelectron spectroscopy (XPS). The thermal properties were analyzed by thermogravimetry (TG). The adsorption capacity was measured and the effect of initial pH was investigated. The results showed that ATP was successfully reacted with CA and the adsorption capacity was enhanced with the increase of the pH value. CA/ATP-g-CDs gel fibers were favorable materials to detect and adsorb MB simultaneously, and MB could be adsorbed by gel fibers and also the fluorescence of CA/ATP-g-CDs was weakened. At low concentrations of MB (1 µg L-1), the removal efficiency could even be as high as 100%.

Comparative analysis of hepatocellular carcinoma and cirrhosis gene expression profiles.

Gene expression data of hepatocellular carcinoma (HCC) was compared with that of cirrhosis (C) to identify critical genes in HCC. A total of five gene expression data sets were downloaded from Gene Expression Omnibus. HCC and healthy samples were combined as dataset HCC, whereas cirrhosis samples were included in dataset C. A network was constructed for dataset HCC with the package R for performing Weighted Gene Co­expression Network Analysis. Modules were identified by cluster analysis with the packages flashClust and dynamicTreeCut. Hub genes were screened out by calculating connectivity. Functional annotations were assigned to the hub genes using the Database for Annotation, Visualization and Integration Discovery, and functional annotation networks were visualized with Cytoscape. Following the exclusion of outlier samples, 394 HCC samples and 47 healthy samples were included in dataset HCC and 233 cirrhosis samples were included in dataset C. A total of 6 modules were identified in the weighted gene co­expression network of dataset HCC (blue, brown, turquoise, green, red and yellow). Modules blue, brown and turquoise had high preservation whereas module yellow exhibited the lowest preservation. These modules were associated with transcription, mitosis, cation transportation, cation homeostasis, secretion and regulation of cyclase activity. Various hub genes of module yellow were cytokines, including chemokine (C­C motif) ligand 22 and interleukin­19, which may be important in the development of HCC. Gene expression profiles of HCC were compared with those of cirrhosis and numerous critical genes were identified, which may contribute to the progression of HCC. Further studies on these genes may improve the understanding of HCC pathogenesis.

The development of methods for the detection of Salmonella in chickens by a combination of immunomagnetic separation and PCRs.

Micro- and nanoimmunomagnetic beads (MIMBs and NIMBs) used for immunomagnetic separation (IMS) with PCR were studied for the rapid detection of Salmonella. The capture efficiency of the two different IMBs was evaluated by a conventional plate counting method, and the binding pattern was studied using scanning electron microscopy. The specificity of the IMBs was tested with Salmonella, Shigella flexneri, enterohemorrhagic Escherichia coli O157:H7, and Listeria monocytogenes. By comparing the pre-enrichment IMS and the IMS enrichment steps with a 5.5-H enrichment time, this study developed a rapid and sensitive method for the detection of Salmonella in chicken. The method was implemented by IMS enrichment and PCR with MIMBs and NIMBs, with a total analysis time of 8 H. We showed that the method was sensitive based on NIMBs with a detection limit of 10° CFU for Salmonella in 25 g of chicken.

A thermoresponsive supramolecular copolymer hydrogel for the embolization of kidney arteries.

Our team has previously reported a high strength thermoplastic supramolecular polymer hydrogel. However, the hydrogel required injection temperatures outside the physiological range therefore preventing its use in a living environment. In this article, we reported a thermoresponsive supramolecular copolymer hydrogel p(N-acryloyl glycinamide-co-acrylamide) (PNAGA-PAAm), which can be injected at temperatures within the physiological range. We used rheological measurements to demonstrate that the transition temperature (upper critical solution temperature) of both the moduli and gel-sol could be finely adjusted by controlling both the ratio and concentration of the monomer. Adding iohexol (contrast agent) in PNAGA-PAAm hydrogels contributed to the decreased moduli and gel-sol transition temperature due to weakening of the hydrogen bonding interactions. The cytocompatible and hemocompatible PNAGA-PAAm sol mixed with iohexol was injected into the renal arteries of rabbits through a microcatheter at a temperature within the high biological range. The transition from the injection temperature (high biological range) to body temperature (basal for the animals) quickly solidified the embolic agent without the occurrence of dehydration, therefore overcoming the main limitation of LCST-typed poly(N-isopropylacrylamide) previously reported. Angiography and histological examination demonstrated the successful embolization of both renal arteries and no recanalization was observed after 8 weeks. The PNAGA-based supramolecular copolymer hydrogel is a novel embolic agent that allows for the occlusion of larger sized arteries in a biocompatible environment.

Nanotheranostics: Congo Red/Rutin-MNPs with Enhanced Magnetic Resonance Imaging and H2O2-Responsive Therapy of Alzheimer's Disease in APPswe/PS1dE9 Transgenic Mice.

As nanotheranostics, Congo red/Rutin-MNPs combine the abilities of diagnosis and treatment of Alzheimer's disease (AD). The biocompatible nanotheranostics system based on iron oxide magnetic nanoparticles, with ultrasmall size and excellent magnetic properties, can specifically detect amyloid plaques by magnetic resonance imaging, realize targeted delivery of AD therapeutic agents, achieve drug controlled release by H2O2 response, and prevent oxidative stress.

Theranostic Gold Nanomicelles made from Biocompatible Comb-like Polymers for Thermochemotherapy and Multifunctional Imaging with Rapid Clearance.

A new generation of photothermal theranostic agents based on assembling 6 nm gold nanoparticles (AuNPs) is developed by using a novel comb-like amphipathic polymer as the template. The small AuNPs are assembled into DOX@gold nanomicelles, which show strong absorbance in the near-infrared region, for multimodal bioimaging and highly effective in vivo chemotherapy and photothermal therapy.

Theranostic self-assembly structure of gold nanoparticles for NIR photothermal therapy and X-Ray computed tomography imaging.

The controllable self-assembly of amphiphilic mixed polymers grafted gold nanoparitcles (AuNPs) leads to strong interparticle plasmonic coupling, which can be tuned to the near-infrared (NIR) region for enhanced photothermal therapy (PTT). In this study, an improved thiolation method was adopted for ATRP and ROP polymer to obtain amphiphilic brushes of PMEO2MA-SH and PCL-SH. By anchoring PCL-SH and PMEO2MA-SH onto the 14 nm AuNPs, a smart hybrid building block for self-assembly was obtained. Increasing the PCL/PMEO2MA chain ratio from 0.8:1, 2:1 and 3:1 to 7:1, the structure of gold assemblies (GAs) was observed to transfer from vesicle to large compound micelle (LCM). Contributed to the special dense packed structure of gold nanoparticles in LCM, the absorption spectrometry of gold nanoparticles drastically red-shifted from 520 nm to 830 nm, which endowed the GAs remarkable NIR photothermal conversion ability. In addition, gold has high X-ray absorption coefficient which qualifies gold nanomaterial a potential CT contrast agent Herein, we obtain a novel gold assembly structure which can be utilized as potential photothermal therapeutic and CT contrast agents. In vitro and In vivo studies testified the excellent treatment efficacy of optimum GAs as a PTT and CT contrast agent. In vitro degradation test, MTT assay and histology study indicated that GAs was a safe, low toxic reagent with good biodegradability. Therefore, the optimum GAs with strong NIR absorption and high X-ray absorption coefficient could be used as a theranostic agent and the formation of novel gold large compound micelle might offers a new theory foundation for engineering design and synthesis of polymer grafted AuNPs for biomedical applications.