Anomalously Shaped Functional Particles Prepared by Thiol-Isocyanate Off-Stoichiometric Click Dispersion Polymerization.

Anomalously shaped microparticles have attractive advantages in applications. They are usually prepared by chain-growth polymerizations in heterogeneous systems. Recently, thiol-X step-growth polymerizations have been used to produce functional particles with a regular shape but rarely anomalous shapes. Herein, we report the preparation of anomalously shaped particles by thiol-isocyanate dispersion polymerization (Dis.P) in ethanol using polyvinylpyrrolidone (PVP) as a stabilizer and catalyst. Papillae-shaped, raspberry-like, and multibulged particles are prepared by tuning monomer combinations, contents, and feed ratios. Particle morphology evolutions during polymerization are observed by scanning electron microscopy (SEM). Distinct from previous works, particles with residual -SH groups are obtained even with equal moles of monomers added initially. The residue of -SH groups is revealed by Fourier transform infrared spectroscopy (FT-IR) analyses and confirmed by detection with a fluorescent probe containing disulfide linkage. Moreover, fluorescent particle probes are formed by the reaction of excess -NCO groups on particles with fluorescein isothiocyanate isomer I (FITC) and dithioacetal-functionalized perylenediimide (DTPDI). The probes are sensitive in detection of glutathione (GSH) and Hg2+ in water. Hg2+ as low as 1-0.1 ppb is detected using a raspberry-like particle probe with DTPDI.

The Ethanolic Extract of Caesalpinia sappan Heartwood Inhibits Cerebral Ischemia/Reperfusion Injury in a Rat Model Through a Multi-Targeted Pharmacological Mechanism.

Background: Caesalpinia sappan L. (C. sappan) is a traditional Chinese medicinal plant. The dried heartwood of C. sappan (also known as Sappan wood) has been widely used for the folkloric medical treatment of ischemic cerebral stroke in China. However, the detailed underlying pharmacological mechanism still remains largely unexplored. Methods: In this study, a middle cerebral artery occlusion (MCAO) rat model was employed to elucidate the mechanism of the anti-cerebral ischemic effects of C. sappan ethanolic extract (CEE). Moreover, systemic multi-target identification coupled with gene ontology biological process (GO BP) and reactome pathway analysis was used to investigate the potential neuroprotective mechanism. Furthermore, the presumed mechanism was confirmed through biological analysis by determining the effects of CEE on the identified signaling pathways in PC12 cells model-induced by oxygen-glucose deprivation/reperfusion (OGD/R). Results: Our study demonstrates that CEE (both through in vivo administration at a dosage of 300 mg/kg and through in vitro incubation at a dosage of 2.4 µg/mL) is a neuroprotective agent that can effectively inhibit neuronal damage, promote synaptic generation, and suppress the activation of neutrophils, microglia, and astrocytes. Moreover, the neuroprotective mechanism of CEE is mediated via regulating 150 potential target proteins, which are associated with 6 biological processes and 10 pathways, including JAK-STAT, HSP90 and DNA damage/telomere stress. Conclusion: CEE can exert neuroprotective effect through multi-target pharmacological mechanisms to prevent ischemia/reperfusion-induced cerebral injury.

[Identification and function analysis of target group for cardioprotection of Baoyuan decoction].

Baoyuan decoction (BYD) is a well-known traditional Chinese medicine formula for coronary heart disease with Qi deficiency. However, the detailed pharmacological mechanism of BYD is still unknown because of its complicated chemical compositions. In this study, we synthesized a kind of solid beads with benzophenone groups on its surface. Benzophenone can be activated and chemically cross-linked with the C-H bonds of the chemical compositions in BYD (BYD beads) under UV activation. We thus captured all the target proteins from mouse heart tissue lysates by using BYD beads. Based on proteomics analysis, we discovered totally 46 potential binding target proteins, most of which were located in mitochondria. KEGG analysis revealed that these target proteins were mainly associated with TCA cycle and amino acid metabolism signaling pathways, suggesting that the cardioprotection of BYD might be associated with regulating mitochondrial function and energy production. Moreover, JC-1 staining analysis also confirmed the protective effect of BYD on mitochondrial damage. In summary, our findings elucidated the potential mechanism of BYD on cardioprotection through "target fishing" strategy, and further explained its traditional efficacy in the molecular level. In addition, we also provide an approach for investigating the target group of complicated compositions in Chinese herbal formula. This novel method may provide a methodological reference for exploring the pharmacological mechanism of traditional Chinese formula in the future.

[Identification and function analysis of neuroprotective targets group of modified Wuzi Yanzong pill].

Targets group identification in complex Chinese medicine system is a key step for revealing the potential mechanism of Chinese medicine. The solid beads with magnetic core and benzophenone-modified surface were made in our study, and then benzophenone was activated and cross-linked with the C-H bonds of chemical compositions in Chinese medicines under UV excitation. Thus the chemical compositions of modified Wuzi Yanzong pill(MWP) were linked to the solid bead surface, and enriched the neuroprotective targets group of MWP after being co-incubated with nerve cell lysate. We performed proteomics analysis on these targets and discovereda total of 32 potential binding targets. KEGG analysis revealed that these targets were mainly associated with Hippo and Cell cycle signaling pathways, suggesting that MWP might be involved in regulating the proliferation and differentiation of neural stem cells. Our findings elucidate the potential targets and mechanism of MWP on anti-dementia and neuroprotection, and further providean approach for investigating the targets group in complex Chinese medicine system. This novel method may provide methodological references for exploring the pharmacological mechanism of Chinese medicinal formulae in the future.

Direct one-pot synthesis of chemically anisotropic particles with tunable morphology, dimensions, and surface roughness.

Previously, synthesis of anisotropic particles by seeded polymerizations has involved multiple process steps. In conventional one-pot dispersion polymerization (Dis.P) with a cross-linker added, only spherical particles are produced due to rapid and high cross-linking. In this Article, a straightforward one-pot preparation of monodisperse anisotropic particles with tunable morphology, dimensions, surface roughness, and asymmetrically distributed functional groups is described. With a cross-linker of divinylbenzene (DVB, 8%), ethylene glycol dimethacrylate (EGDMA, 6%), or dimethacryloyloxybenzophenone (DMABP, 5%) added at 40 min, shortly after the end of nucleation stage in Dis.P of styrene (St) in methanol and water (6/4, vol), the swollen growing particles are inhomogeneously cross-linked at first. Then, at low gel contents of 59%, 49%, and 69%, corresponding to the cases using DVB, EGDMA, and DMABP, respectively, the growing particle phase separates and snowman- or dumbbell-like particles are generated. Thermodynamic and kinetic analyses reveal that moderate cross-linking and sufficient swelling of growing particles determine the formation and growth of anisotropic particles during polymerization. Morphology, surface roughness, sizes, and cross-linking degrees of each domain of final particles are tuned continuously by varying start addition time and contents of cross-linkers. The snowman-like particles fabricated with DVB have a gradient cross-linking and asymmetrical distribution of pendant vinyl groups from their body to head. The dumbbell-like particles prepared using DMABP have only one domain cross-linked; i.e., only one domain contains photosensitive benzophenone (BP) groups. With addition of glycidyl methacrylate (GMA) or propargyl methacrylate (PMA) together with DVB or EGDMA, epoxy or alkynyl groups are asymmetrically incorporated. With the aid of these functional groups, carboxyl, amino, or thiol groups and PEG (200) are attached by thiol-ene (yne) click and photocoupling reactions.

Facile synthesis of core-shell/hollow anisotropic particles via control of cross-linking during one-pot dispersion polymerization.

Preparation of anisotropic particles based on seed phase separation involves multiple processes, and asymmetrical structures and surfaces cannot be produced when anisotropic shapes emerge. In conventional one-pot dispersion polymerization (Dis.P) using cross-linker, only spherical particles are prepared due to rapid and high cross-linking. Herein, monodisperse snowman-like particles with core-shell/hollow structures and partially rough surface were synthesized straightforward by a modified one-pot Dis.P, in which ethylene glycol and water (6/4, vol.) were used as medium, and ammonium persulfate (APS) aqueous solution, vinyl acetate (VA) and/or acrylic acid (AA), divinylbenzene (DVB) and styrene (St) were added at 6h. The cross-linking of growing particles was confined to exterior (forming cross-linked shell), and gel contents were low, leading to phase separation. Asymmetrical morphologies, structures, sizes and surface roughness were flexibly tuned by varying amounts of APS, VA and/or AA, water and DVB, and DVB adding speed. At low APS contents or high DVB amounts, the inhomogeneous cross-linking of head enabled its phase to separate, producing elongated head. With addition of VA and AA, phase separations inside head and body were induced, generating hollow structure. Adding DVB very slowly, nonlinear growth of third compartment occurred, forming bowed head.

Photoreactive, core-shell cross-linked/hollow microspheres prepared by delayed addition of cross-linker in dispersion polymerization for antifouling and immobilization of protein.

When dispersion polymerization of styrene (St) had run for 3h, after particle rapidly growing stage, 4,4'-dimethacryloyloxybenzophenone (DMABP) cross-linker was added to reaction system and photoreactive, core(PSt)-shell(Poly(St-co-DMABP)) particles with rich benzophenone (BP) groups on surface were prepared. Polymerization of DMABP could occurred mainly on the preformed core of PSt because its diffusion could be impeded by (1) compactness of particles formed at the moment of cross-linker addition (more than 80% of monomer had been consumed, particles were no longer fully swollen by monomer), (2) reduced polarity of continuous phase, and (3) immediate occurrence of cross-linking. Subsequently, photoreactive, cross-linked hollow particles were yielded by removal of uncross-linked core in THF. SEM and TEM observation demonstrated the formation of core-shell structure and improvement of shell thickness when DMABP content increased. UV-vis spectra analysis on polymer dissolved in THF indicated that there is no polymer of DMABP in core. FTIR spectra analysis and XPS measurement further revealed that BP component on particle surface was enriched when amount of DMABP increased. Finally, an anti-fouling polymer (poly (ethylene glycol), PEG) and protein of mouse IgG was immobilized on particle surface under UV irradiation, as confirmed by FTIR spectra analysis, SEM observation and TMB color reaction.

Direct observations of three nucleation/growth processes of charge-stabilized dispersion polymerizations with varying water/methanol ratios.

This article presents observations of three polymerization modes of a self-developed cation-charge-stabilized styrene/water/methanol dispersion polymerization system: (1) a water/methanol (20/80) system, corresponding to a typical dispersion polymerization mode where the particle nucleation occurred in the solution phase and growth in the particle phase; (2) a pure CH(3)OH system, including a first nucleation in the solution phase with growth by absorption of the small particles and polymers formed in this phase, and a secondary nucleation with growth in the particle phase, when high molecular weight copolymers appeared in the solution phase; and (3) a water/methanol (5/95) system, similar to the conventional dispersion polymerization mode during the first 90 min, with subsequent epitaxial growth. Interestingly, the metastable state of the nucleation stage, including minuscule 6-nm particles, their aggregates, and the aggregating process, was first observed experimentally. By quantitatively following the relationship of the deposited molecular weight and the nucleation/growth process in the three systems, it was proposed that the molecular weight of the deposited polymer had to reach a specific high value before they could absorb or capture monomer to form smooth/spherical nuclei or particles.

Preparation of soft hydrogel nanoparticles with PNIPAm hair and characterization of their temperature-induced aggregation.

There exists a great number of publications concerning the synthesis of core-shell and/or hairy particles by means of controlled/living polymerization. Nevertheless, how to fabricate ultrafine nanosized hairy particles, especially polymeric soft hairy particles, remains a significant challenge. This paper presents a simple self-developed approach consisting of a two-step photoinduced polymerization of cross-linked polyacrylamide (CLPAM) soft hydrogel nanoparticles (5-10 nm in diameter) grafted with poly(N-isopropylacrylamide) (PNIPAm) chains. The architecture of such ultrafine soft water-swollen CLPAM@PNIPAm core/shell nanoparticles (20-35 nm in diameter) demonstrated very specific temperature sensitive behaviors. During heating a fast association process was observed at approximately 33-34 degrees C and the singular hairy particles with 34 nm diameters clustered into aggregates that were approximately 120 nm in diameter. Raising the temperature further, however, led to a decrease in size to about 100 nm at 45 degrees C. This behavior was attributed to the formation of hydrophobic shell layers accompanying the shrinkage of PNIPAm chains with chain polar transformations. With the contraction pressure produced by further shrinkage of the hydrophobic shell layers, the soft fully swollen PAM cores expelled water and diminished in size. During the cooling process, these contracted cores that were trapped in the aggregates gave rise to an early dissociation. The hydrophilic hairy CLPAM@PNIPAm particles are believed to be potentially useful as carriers to specific target regions, e.g., cells for controlled drug delivery and other smart biomaterial applications.

Preparation of polymeric Janus particles by directional UV-induced reactions.

Polymeric Janus particles are obtained by UV-induced selective surface grafting polymerizations and coupling reactions, in virtue of the light-absorption of photoreactive materials such as the immobilized photoinitiator and spread photoinitiator solution on the surfaces exposed to UV light and the sheltering of densely arrayed immovable particles from light. Varying the monomers or macromolecules applied in photografting polymerization or coupling reaction, and choosing diverse polymeric particles of various size, bicolor and amphiphilic Janus particles could be successfully achieved. Observations by fluorescence microscope, scanning electron microscope ,and transmission electron microscope confirmed the asymmetrical morphology of the resultant Janus particles.

Fabrication of a molecular-level multilayer film on organic polymer surfaces via chemical bonding assembly.

A fresh multilayer film was fabricated on a molecular level and successfully tethered to the surface of a hydroxylated organic substrate via chemical bonding assembly (CBA). Sulfate anion groups (SO4-) were preintroduced onto the surface of biaxially oriented polypropylene (BOPP) films via a reference method. Upon hydrolysis of the SO4- groups, hydroxyl groups (--OH) were formed that subsequently acted as initial reagents for a series of alternate reactions with terephthalyl chloride (TPC) and bisphenol A (BPA). A stable and well-defined multilayer film was thus fabricated via the CBA method. As a result of the nanoscale multilayer fresh film being abundant with reactive groups, it is believed that the film and its fabrication method should provide a fundamental platform for further surface functionalization and direct the design of advanced materials with desired properties.

Fluorescence quenching of bovine serum albumin.

The fluorescence emission spectra and 3D fluorescence spectra of bovine serum albumin (BSA) in cetyltrimethylammonium bromide (CTAB) reversed micelles were affected by the microenvironment. Blue shifts of the fluorescence emission peaks were found when BSA was present in CTAB reversed micelles. The fluorescence intensity changed with the water content. Similar changes in the peak regions of the 3D fluorescence spectra were also observed. CdS nanoparticles prepared in CTAB reversed micelles quenched the fluorescence of BSA significantly. The fluorescence of BSA was more effectively quenched by negative CdS nanoparticles than by positive or neutral CdS ones. The quenching degree increased linearly with increasing the concentration of negative CdS nanoparticles over the range of 5.0 x 10(-6) - 3.0 x 10(-5) mol L(-1). The quenching mechanism is discussed and the quenching constant is 1.32 x 10(4) L mol(-1).