A Sequence-Defined ABC Dendritic Macromolecule with Amino Acid Peripheral Functionality via Iterative Chemoselective Reactions.

Chemoselective reactions allow near-precision control over the polymer composition and topology to create sequence-controlled polymers with similar secondary and tertiary structures to those found in proteins. Dendrimers are recognized as well-defined macromolecules with the potential to mimic protein surface functionality due to the large number of functional groups available at its periphery with the internal structure acting as the support scaffold. Transitioning from using small-molecule dendrimers to dendritic macromolecules will not only allow retention of the high peripheral functionality but also provide an internal scaffold with a desired polymer composition within each generational layer. Here, we exemplify a systematic approach to creating a dendritic macromolecule with the placement of different polymer building blocks in precise locations within the internal structure and the placement of three different amino acid moieties clustered at the periphery. The synthesis of this ABC dendritic macromolecule was accomplished through iterative chemoselective reactions.

Interfacial Colloidal Self-Assembly for Functional Materials.

ConspectusSelf-assembly bridges nanoscale and microscale colloidal particles into macroscale functional materials. In particular, self-assembly processes occurring at the liquid/liquid or solid/liquid/air interfaces hold great promise in constructing large-scale two- or three-dimensional (2D or 3D) architectures. Interaction of colloidal particles in the assemblies leads to emergent collective properties not found in individual building blocks, offering a much larger parameter space to tune the material properties. Interfacial self-assembly methods are rapid, cost-effective, scalable, and compatible with existing fabrication technologies, thus promoting widespread interest in a broad range of research fields.Surface chemistry of nanoparticles plays a predominant role in driving the self-assembly of nanoparticles at water/oil interfaces. Amphiphilic nanoparticles coated with mixed polymer brushes or mussel-inspired polydopamine were demonstrated to self-assemble into closely packed thin films, enabling diverse applications from electrochemical sensors and catalysis to surface-enhanced optical properties. Interfacial assemblies of amphiphilic gold nanoparticles were integrated with graphene paper to obtain flexible electrodes in a modular approach. The robust, biocompatible electrodes with exceptional electrocatalytic activities showed excellent sensitivity and reproducibility in biosensing. Recyclable catalysts were prepared by transferring monolayer assemblies of polydopamine-coated nanocatalysts to both hydrophilic and hydrophobic substrates. The immobilized catalysts were easily recovered and recycled without loss of catalytic activity. Plasmonic nanoparticles were self-assembled into a plasmonic substrate for surface-enhanced Raman scattering, metal-enhanced fluorescence, and modulated fluorescence resonance energy transfer (FRET). Strong Raman enhancement was accomplished by rationally directing the Raman probes to the electromagnetic hotspots. Optimal enhancement of fluorescence and FRET was realized by precisely controlling the spacing between the metal surface and the fluorophores and tuning the surface plasmon resonance wavelength of the self-assembled substrate to match the optical properties of the fluorescent dye.At liquid/solid interfaces, infiltration-assisted (IFAST) colloidal self-assembly introduces liquid infiltration in the substrate as a new factor to control the degree of order of the colloidal assemblies. The strong infiltration flow leads to the formation of amorphous colloidal arrays that display noniridescent structural colors. This method is compatible with a broad range of colloidal particle inks, and any solid substrate that is permeable to dispersing liquids but particle-excluding is suitable for IFAST colloidal assembly. Therefore, the IFAST technology offers rapid, scalable fabrication of structural color patterns of diverse colloidal particles with full-spectrum coverage and unprecedented flexibility. Metal-organic framework particles with either spherical or polyhedral morphology were used as ink particles in the Mayer rod coating on wettability patterned photopapers, leading to amorphous photonic structures with vapor-responsive colors. Anticounterfeiting labels have also been developed based on the complex optical features encoded in the photonic structures.Interfacial colloidal self-assembly at the water/oil interface and IFAST assembly at the solid/liquid/air interface have proven to be versatile fabrication platforms to produce functional materials with well-defined properties for diverse applications. These platform technologies are promising in the manufacturing of value-added functional materials.

Recent advances in responsive antibacterial materials: design and application scenarios.

Bacterial infection is one of the leading causes of death globally, although modern medicine has made considerable strides in the past century. As traditional antibiotics are suffering from the emergence of drug resistance, new antibacterial strategies are of great interest. Responsive materials are appealing alternatives that have shown great potential in combating resistant bacteria and avoiding the side effects of traditional antibiotics. In this review, the responsive antibacterial materials are introduced in terms of stimulus signals including intrinsic (pH, enzyme, ROS, etc.) and extrinsic (light, temperature, magnetic fields, etc.) stimuli. Their biomedical applications in therapeutics and medical devices are then discussed. Finally, the author's perspective of the challenge and the future of such a system is provided.

Caging Cationic Polymer Brush-Coated Plasmonic Nanostructures for Traceable Selective Antimicrobial Activities.

Cationic polymers are under intense research to achieve prominent antimicrobial activity. However, the cellular and in vivo toxicity caused by nonspecific electrostatic interaction has become a major challenge for their practical applications. Here, the development of a "caging" strategy based on the use of a block copolymer consisting of a stealth block and an anionic block that undergoes degradation in presence of enzymes secreted by selective bacterial pathogens of interest is reported. The results have shown that antimicrobial cationic polymer brushes-coated gold nanorods (AuNRs) can be caged by the block polymer of poly(ethylene glycol) and anionic, lipase-degradable block of ε-caprolactone and methacrylic acid copolymer to afford neutrally charged surfaces. The caged AuNRs are activated by lipase released by bacteria of interest to endow an excellent bactericidal effect but show minimal binding and toxicity against mammalian cells and nonspecific bacteria that do not produce lipase. In this design, AuNRs play multifunctional roles as the scaffolds for polymer brushes, photothermal transducers, and imaging probes for traceable delivery of the activation and delivery of bactericidal cationic polymer brushes. The caging strategy opens new opportunities for the safe delivery of antimicrobial materials for the treatment of bacterial infections.

Magnetic nanochains-based dynamic ELISA for rapid and ultrasensitive detection of acute myocardial infarction biomarkers.

Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality globally. The serum levels of a group of cardiac biomarkers have been regarded as important indicators in the routine diagnosis of AMI. The development of rapid, sensitive, and accurate detection methods of AMI biomarkers is urgently needed for the early diagnosis of AMI. Here, a dynamic and pseudo-homogeneous enzyme-linked immunosorbent assay (ELISA) was reported based on the combined use of bioconjugated magnetic nanochains (MNCs) and gold nanoparticles (AuNPs) probes. The capture antibodies-conjugated MNCs served as dynamic nano-mixers to facilitate liquid mixing and as homogeneously dispersed capturing agents to capture and separate specific targets. The AuNPs probes were prepared by co-immobilization of detection antibodies and horseradish peroxidase (HRP) for signals amplification. The design of bioconjugated MNCs and AuNPs probes significantly increased the assay kinetics and improves the assay sensitivity. This novel ELISA strategy realized accurate detection of a panel of AMI biomarkers within 35 min, leading to considerably improved sensitivities compared to that of conventional ELISA method.

Metabolic Labeling Mediated Targeting and Thermal Killing of Gram-Positive Bacteria by Self-Reporting Janus Magnetic Nanoparticles.

Nanoparticles have been widely used in detection and killing of bacteria; however, targeting bacteria is still challenging. Delicate design of nanoparticles is required for simultaneous targeting, detection, and therapeutic functions. Here the use of Au/MnFe2 O4 (Au/MFO) Janus nanoparticles to target Gram-positive bacteria via metabolic labeling is reported and realize integrated self-reporting and thermal killing of bacteria. In these nanoparticles, the Au component is functionalized with tetrazine to target trans-cyclooctene group anchored on bacterial cell wall by metabolic incorporation of d-amino acids, and the MFO part exhibits peroxidase activity, enabling self-reporting of bacteria before treatment. The spatial separation of targeting and reporting functions avoids the deterioration of catalytic activity after surface modification. Also important is that MFO facilitates magnetic separation and magnetic heating, leading to easy enrichment and magnetic thermal therapy of labeled bacteria. This method demonstrates that metabolic labeling with d-amino acids is a promising strategy to specifically target and kill Gram-positive bacteria.

Ultrathin Aramid/COF Heterolayered Membrane for Solid-State Li-Metal Batteries.

Ultrathin, ultrastrong, and highly conductive solid-state polymer-based composite electrolytes have long been exploited for the next-generation lithium-based batteries. In particular, the lightweight membranes that are less than tens of microns are strongly desired, aiming to maximize the energy densities of solid-state batteries. However, building such ideal membranes are challenging when using traditional materials and fabrication technologies. Here we reported a 7.1 µm thick heterolayered Kevlar/covalent organic framework (COF) composite membrane fabricated via a bottom-up spin layer-by-layer assembly technology that allows for precise control over the structure and thickness of the obtained membrane. Much stronger chemical/mechanical interactions between cross-linked Kevlar and conductive 2D-COF building blocks were designed, resulting in a highly strong and Li+ conductive (1.62 × 10-4 S cm-1 at 30 °C and 4.6 × 10-4 S cm-1 at 70 °C) electrolyte membrane that can prevent solid-state batteries from short-circuiting after over 500 h of cycling. All-solid-state lithium batteries using this membrane enable a significantly improved energy density.

Polymeric Sulfur as a Li Ion Conductor.

The typical polymer electrolyte matrix has been limited to the chains consisting of -C-C- or -C-O-C- or -Si-O- backbone with different solvating groups for decades. In this work, the polymeric sulfur consisting of -(S-S)n- backbone with a high sulfur content (up to 90 wt % S) was reported for the first time. The flexible -(S-S)n- chains with high S atom density create an intense "solvating" environment for Li+ conduction, achieving an excellent Li+ conductivity of 1.69 × 10-3 S cm-1 at 80 °C. Benefiting from its unique thermoplasticity, a hot-rolling process was also developed for fabricating the poly-S membrane. The symmetric solid-state Li cell using the membrane showed a high cycling stability over 300 h. The work offers a novel platform for chemists to design new polymer electrolytes that are quite different with conventional carbon-based polymer electrolytes.

A Self-Assembled Plasmonic Substrate for Enhanced Fluorescence Resonance Energy Transfer.

Fluorescence resonance energy transfer (FRET) has found widespread uses in biosensing, molecular imaging, and light harvesting. Plasmonic metal nanostructures offer the possibility of engineering photonic environment of specific fluorophores to enhance the FRET efficiency. However, the potential of plasmonic nanostructures to enable tailored FRET enhancement on planar substrates remains largely unrealized, which are of considerable interest for high-performance on-surface bioassays and photovoltaics. The main challenge lies in the necessitated concurrent control over the spectral properties of plasmonic substrates to match that of fluorophores and the fluorophore-substrate spacing. Here, a self-assembled plasmonic substrate based on polydopamine (PDA)-coated plasmonic nanocrystals is developed to effectively address this challenge. The PDA coating not only drives interfacial self-assembly of the nanocrystals to form closely packed arrays with customized optical properties, but also can serve as a tailored nanoscale spacer between the fluorophores and plasmonic nanocrystals, which collectively lead to optimized fluorescence enhancement. The biocompatible plasmonic substrate that allows convenient bioconjugation imparted by PDA has afforded improved FRET efficiency in DNA microarray assay and FRET imaging of live cells. It is envisioned that the self-assembled plasmonic substrates can be readily integrated into fluorescence-based platforms for diverse biomedical and photoconversion applications.

Functional Macromolecule-Enabled Colloidal Synthesis: From Nanoparticle Engineering to Multifunctionality.

The synthesis of well-defined inorganic colloidal nanostructures using functional macromolecules is an enabling technology that offers the possibility of fine-tuning the physicochemical properties of nanomaterials and has contributed to a broad range of practical applications. The utilization of functional reactive polymers and their colloidal assemblies leads to a high level of control over structural parameters of inorganic nanoparticles that are not easily accessible by conventional methods based on small-molecule ligands. Recent advances in polymerization techniques for synthetic polymers and newly exploited functions of natural biomacromolecules have opened up new avenues to monodisperse and multifunctional nanostructures consisting of integrated components with distinct chemistries but complementary properties. Here, the evolution of colloidal synthesis of inorganic nanoparticles is revisited. Then, the new developments of colloidal synthesis enabled by functional macromolecules and practical applications associated with the resulting optical, catalytic, and structural properties of colloidal nanostructures are summarized. Finally, a perspective on new and promising pathways to novel colloidal nanostructures built upon the continuous development of polymer chemistry, colloidal science, and nanochemistry is provided.

Polymer Electrolyte Glue: A Universal Interfacial Modification Strategy for All-Solid-State Li Batteries.

In recent years solid Li+ conductors with competitive ionic conductivity to those of liquid electrolytes have been reported. However, the incorporation of highly conductive solid electrolytes into the lithium-ion batteries is still very challenging mainly due to the high resistance existing at the solid-solid interfaces throughout the battery structure. Here, we demonstrated a universal interfacial modification strategy through coating a curable polymer-based glue electrolyte between the electrolyte and electrodes, aiming to address the poor solid-solid contact and thus decrease high interfacial resistance. The liquid glue exhibits both great wettability as well as chemical/electrochemical stability to most of the electrodes, and it can be easily solidified into a polymer electrolyte layer through a "post-curing" treatment. As a result, symmetric Li batteries with the glue modification exhibit much smaller impedance and enhanced stability upon plating/stripping cycles compared to the batteries without glue modification. The all-solid-state Li-S batteries with glue modification show significantly enhanced performances. The strategy of developing glue electrolytes to improve the electrode-electrolyte interface contact provides an alternative option for improving many other solid-state batteries.

Self-Assembly of Polymer-Coated Plasmonic Nanocrystals: From Synthetic Approaches to Practical Applications.

Self-assembly of plasmonic nanocrystals (PNCs) and polymers provides access to a variety of functionalized metallic-polymer building blocks and higher-order hybrid plasmonic assemblies, and thus is of considerable fundamental and practical interest. The hybrid assemblies often not only inherit individual characteristics of polymers and PNCs but also exhibit distinct photophysical and catalytic properties compared to that of a single PNC building block. The tailorable plasmonic coupling between PNCs within assemblies enables the precise control over localized surface plasmon resonance, which subsequently affords a series of light-driven or photo-activated applications, such as surface-enhanced Raman scattering detection, photoacoustic imaging, photothermal therapy, and photodynamic therapy. In this review, the synthetic strategies of a library of PNC-polymer hybrid building blocks and corresponding assemblies are summarized along with the mechanisms of polymer-assisted self-assembly of PNCs and the concepts for bridging the intrinsic properties of PNC-polymer assemblies to widespread practical applications.

Influence of Constraints within a Cyclic Polymer on Solution Properties.

Cyclic polymers with internal constraints provide new insight into polymer properties in solution and bulk and can serve as a model system to explain the stability and mobility of cyclic biomacromolecules. The model system used in this work consisted of cyclic polystyrene structures, all with a nearly identical molecular weight, designed with 0-3 constraints located at strategic sites within the cyclic polymer, with either 4 or 6 branch points. The total number of branch points (or arms) within the cyclic ranged from 0 to 18. Molecular dynamic (MD) simulations showed that as the number of arms increased within the cyclic structure, the radius of gyration and the hydrodynamic radius generally decreased, suggesting the greater number of constraints resulted in a more compact polymer chain. The simulations further showed that the excluded volume was much greater for the cyclics compared to a linear polymer at the same molecular weight. The spirocyclic, a structure consisting of three rings joined in series, showed significant excluded volume effects in agreement with experimental data; the reason for which is unclear at this stage. Interestingly, under a size exclusion chromatography flow, the radius of hydration for all the cyclic structures increased compared with the DLS data, and could be explained from the greater swelling of the rings perpendicular to the flow found from previous simulations on rings. This data suggests that the greater compactness, greater excluded volume and structural rearrangements under flow of constrained cyclic polymers could be used to provide a physical basis for understanding greater stability and activity of cyclic biological macromolecules.

Peptidomimetic Star Polymers for Targeting Biological Ion Channels.

Four end-functionalized star polymers that could attenuate the flow of ionic currents across biological ion channels were first de novo designed computationally, then synthesized and tested experimentally on mammalian K+ channels. The 4-arm ethylene glycol conjugate star polymers with lysine or a tripeptide attached to the end of each arm were specifically designed to mimic the action of scorpion toxins on K+ channels. Molecular dynamics simulations showed that the lysine side chain of the polymers physically occludes the pore of Kv1.3, a target for immuno-suppression therapy. Two of the compounds tested were potent inhibitors of Kv1.3. The dissociation constants of these two compounds were computed to be 0.1 µM and 0.7 µM, respectively, within 3-fold to the values derived from subsequent experiments. These results demonstrate the power of computational methods in molecular design and the potential of star polymers as a new infinitely modifiable platform for ion channel drug discovery.

Upregulation of p­Akt by glial cell line­derived neurotrophic factor ameliorates cell apoptosis in the hippocampus of rats with streptozotocin­induced diabetic encephalopathy.

The loss of neurotrophic factor support has been shown to contribute to the development of the central nervous system. Glial cell line­derived neurotrophic factor (GDNF), a potent neurotrophic factor, is closely associated with apoptosis and exerts neuroprotective effects on numerous populations of cells. However, the underlying mechanisms of these protective effects remain unknown. In the present study, a significant increase in Bax levels and DNA fragmentation was observed in the hippocampus obtained from the brains of diabetic rats 60 days after diabetes had been induced. The apoptotic changes were correlated with the loss of GDNF/Akt signaling. GDNF administration was found to reverse the diabetes­induced Bax and DNA fragmentation changes. This was associated with an improvement in the level of p­Akt/Akt. In addition, combination of GDNF with a specific inhibitor of the phosphoinositide 3­kinase (PI3K)/Akt pathway, Wortmannin, significantly abrogated the effects of GDNF on the levels of p­Akt/Akt, Bax and DNA fragmentation. However, a p38 mitogen­activated proten kinase (MAPK) inhibitor, SB203580, had no effect on the expression of p­Akt/Akt, Bax or DNA fragmentation. These results demonstrate the pivotal role of GDNF as well as the PI3K/Akt pathway, but not the MAPK pathway, in the prevention of diabetes­induced neuronal apoptosis in the hippocampus.

Induction of Tca8113 tumor cell apoptosis by icotinib is associated with reactive oxygen species mediated p38-MAPK activation.

Icotinib, a selective EGFR tyrosine kinase inhibitor (EGFR-TKI), has been shown to exhibit anti-tumor activity against several tumor cell lines. However, the exact molecular mechanism of icotinib's anti-tumor effect remains unknown. This study aims to examine the zytotoxic effect of icotinib on Tca8113 cells and its potential molecular mechanism. Icotinib significantly resulted in dose-dependent cell death as determined by MTT assay, accompanied by increased levels of Bax and DNA fragmentation. Icotinib could also induce Reactive Oxygen Species (ROS) generation. Further studies confirmed that scavenging of reactive oxygen species by N-acetyl-L-cysteine (NAC), and pharmacological inhibition of MAPK reversed icotinib-induced apoptosis in Tca8113 cells. Our data provide evidence that icotinib induces apoptosis, possibly via ROS-mediated MAPK pathway in Tca8113 cells.

Icotinib inhibits the invasion of Tca8113 cells via downregulation of nuclear factor κB-mediated matrix metalloproteinase expression.

Icotinib is an epidermal growth factor receptor tyrosine kinase inhibitor, which has been revealed to inhibit proliferation in tumor cells. However, the effect of icotinib on cancer cell metastasis remains to be explained. This study examines the effect of icotinib on the migration and invasion of squamous cells of tongue carcinoma (Tca8113 cells) in vitro. The results of the Boyden chamber invasion assay demonstrated that icotinib reduced cell invasion, suppressed the protein levels of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, and increased the expression of tissue inhibitor of metalloproteinase-1. In addition, icotinib was found to significantly decrease the protein levels of nuclear factor κB (NF-κB) p65, which suggested that icotinib inhibits NF-κB activity. Furthermore, treatment with the NF-κB inhibitor, pyrrolidine dithiocarbamate, suppressed cell invasion and MMP-2 expression. These results suggested that icotinib inhibits the invasion of Tca8113 cells by downregulating MMP via the inactivation of the NF-κB signaling pathways.

Glass Transition Temperature of Cyclic Stars.

Cyclic homo- and diblock copolymers with different topologies were synthesized using a combination of "living" radical polymerization and "click" coupling reactions. The topologies included 2- and 3-arm stars, with the arms consisting of either cyclic or linear polystyrene. In addition, a diblock consisting of a cyclic polystyrene and a cyclic poly(acrylic acid) was also made. The topologies by imposing topological constraints due to the presence of cyclic polymers and branch points had a marked influence on the glass transition temperature (Tg). It was found that for the polystyrene topology series, the Tg increased above the glass transition temperature at infinite molecular weight for a linear chain (i.e., Tg∞) and correlated to the more compact nature of cyclic polymers. For the cyclic diblock of polystyrene and poly(acrylic acid), the Tg increased significantly due to separation of the blocks into their pure phases. This resulted in significant stretching of the chains and thus loss of conformation entropy.

[Determination of ascitic bacterial 16S rRNA by quantitative PCR-microarray in the diagnosis of spontaneous bacterial peritonitis].

OBJECTIVE: To evaluate the significance of determining ascitic bacterial 16S rRNA by quantitative PCR combined with microarray (PCR-microarray) in the diagnosis of spontaneous bacterial peritonitis (SBP). METHODS: Ascitic bacterial 16SrRNA was determined by real time fluorescent quantitative PCR-microarray in 76 cases of suspected SBP and 6 cases of non-infectious ascites with chronic liver diseases. The results were compared with ascitic bacterial culture simultaneously. RESULTS: Of 76 ascitic samples, 17 were detected bacteria positive by PCR-microarray, including 8 Grams positive(G+) and 9 Grams negative(G-), which was higher than that by bacterial culture which had only 6 ascitic samples detected positive (all G-); the positive rates were 22.4% vs 7.9%, respectively (P < 0.01). The bacterial strains detected by both methods in 6 cases had a consistency with each other. No bacteria were detected in another 6 cases of non-infectious ascites with chronic liver diseases. CONCLUSIONS: Determination of ascitic bacteria 16S rRNA by PCR-microarray has a higher specificity and sensitivity in the diagnosis of SBP as compared with the bacteria culture. Application of this novel method can not only accelerate SBP diagnosis but also stratify the different pathogens.

[Determination of ascitic bacterial 16S rRNA gene in the rapid diagnosis of spontaneous bacterial peritonitis].

OBJECTIVE: To evaluate the value of ascitic bacterial 16S rRNA gene determination in the rapid diagnosis of spontaneous bacterial peritonitis (SBP). METHODS: 16S rRNA gene from bacterial DNA in ascites was determined by quantitative fluorescent polymerase chain reaction (PCR) in 76 patients with suspected SBP and 6 patients with non-infectious ascites. The results were compared with those obtained from bacterial culture. RESULTS: The positive rate of SBP was 22.4% among patients detected with ascitic bacterial 16S rRNA gene determination-based quantitative fluorescent PCR, which was significantly higher than that (7.9%) in patients only received bacterial culture (P<0.05). In addition,in 6 patients with non-infectious ascites,both the 16S rRNA gene determination-based quantitative fluorescent PCR and bacterial culture showed negative results. CONCLUSIONS: 16S rRNA gene determination-based quantitative fluorescent PCR can be an effective tool for the rapid diagnosis of SBP. It is more sensitive than the bacterial culture.