Protamine‐Capped Mesoporous Silica Nanoparticles for Biologically Triggered Drug Release

The fabrication of a mesoporous silica nanoparticle (MSN)?protamine hybrid system (MSN?PRM) is reported that selectively releases drugs in the presence of specific enzyme triggers present in the proximity of cancer cells. The enzyme trigger involved is a protease called trypsin, which is overexpressed in certain specific pathological conditions, such as inflammation and cancer. Overexpression of trypsin is known to be associated with invasion, metastasis, and growth in several cancers, such as leukemia, colon cancer, and colorectal cancer. The current system (MSN–PRM) consists of an MSN support in which mesopores are capped with an FDA‐approved peptide drug protamine, which effectively blocks the outward diffusion of the drug molecules from the mesopores of the MSNs. On exposure to the enzyme trigger, the protamine cap disintegrates, opening up the molecular gates and releasing the entrapped drug molecules. The system exhibits minimal premature release in the absence of the trigger and selectively releases the encapsulated drugs in the presence of the proteases secreted by colorectal cancer cells. The ability of the MSN–PRM particles to deliver anticancer drugs to colorectal cancer cells has also been demonstrated. The hydrophobic drug is released into cancer cells subsequent to disintegration of the protamine cap, resulting in cell death. Drug‐induced cell death in colorectal cancer cells is significantly enhanced when the hydrophobic drug that is known to degrade in aqueous environments is encapsulated in the MSN–PRM system in comparison to the free drug (P < 0.05). The system, which shows good biocompatibility and selective drug release, is a promising platform for cancer specific drug delivery.     

Emulsion Polymerization of Styrene Mediated by TEMPO at Low Temperature

NMRP is a controlled polymerization technique with the ability to produce polymers with a highly controlled microstructure. The properties of the thus obtained polymers make it desirable to scale this technique to an industrial level, but there are still some challenges to be faced, e.g., to develop emulsion NMRP at low temperatures (lower than about 100 °C) with inexpensive, commercially available nitroxides such as TEMPO. Here, the emulsion NMRP of styrene using TEMPO at temperatures lower than 100 °C is described. An optimal control of molecular weights and polydispersities and a fast polymerization rate are obtained.

     

Combining Modular Ligation and Supramolecular Self‐Assembly for the Construction of Star‐Shaped Macromolecules

A well‐defined random copolymer of styrene (S) and chloromethylstyrene (CMS) featuring lateral chlorine moieties with an alkyne terminal group is prepared (P(S‐co‐CMS), = 5500 Da, PDI = 1.13). The chloromethyl groups are converted into Hamilton wedge (HW) entities (P(S‐co‐HWS), = 6200 Da, PDI = 1.13). The P(S‐co‐HWS) polymer is subsequently ligated with tetrakis(4‐azidophenyl)methane to give HW‐functional star‐shaped macromolecules (P(S‐co‐HWS))₄, = 25 100 Da, PDI = 1.08). Supramolecular star‐shaped copolymers are then prepared via self‐assembly between the HW‐functionalized four‐arm star‐shaped macromolecules ( P(S‐co‐HW )) ₄ and cyanuric acid (CA) end‐functionalized PS (PS–CA, = 3700 Da, PDI = 1.04), CA end‐functionalized poly(methyl methacrylate) (PMMA–CA, = 8500 Da, PDI = 1.13) and CA end‐functionalized polyethylene glycol (PEG–CA, = 1700 Da, PDI = 1.05). The self‐assembly is monitored by ¹H NMR spectroscopy and light scattering analyses.     

1,1′-Dimethylferrocene Mediated L-Glutamate Electrodes Modified With Electropolymerized 1,3-Diaminobenzene Film

Abstract

A mediated L-glutamate biosensor was constructed by incorporating 1,1′-dimethylferrocene in electropolymerized 1,3-diaminobenzene and immobilizing L-glutamate oxidase on the electropolymerized film. Stabilizers (1% DEAE-dextran, 1% MgCl₂ and 10% sucrose) were added to the immobilized enzyme to improve the long-term storage stability. The electrode responded linearly to L-glutamate concentration between 0.1 and 2.0 mM and the response of the electrode did not interfere with electroactive species and oxygen. The useful lifetime of the sensor was at least 3 weeks. When stored in dry form at 28°C, the sensor with stabilizers was stable at least 6 months. The electrode was applied to determine L-glutamate in fermentation broth samples. Good correlations were achieved between results obtained with the sensor and by enzymatic analysis using glutamate dehydrogenase.     

On the Nitroxide Quasi‐Equilibrium in the Alkoxyamine‐Mediated Radical Polymerization of Styrene

Summary: The range of validity of two popular versions of the nitroxide quasi‐equilibrium (NQE) approximation used in the theory of kinetics of alkoxyamine mediated styrene polymerization, are systematically tested by simulation comparing the approximate and exact solutions of the equations describing the system. The validity of the different versions of the NQE approximation is analyzed in terms of the relative magnitude of (dN/dt)/(dP/dt). The approximation with a rigorous NQE, k_c[P][N] = k_d[P N], where P, N and P N are living, nitroxide radicals and dormant species respectively, with kinetic constants k_c and k_d, is found valid only for small values of the equilibrium constant K (10⁻¹¹–10⁻¹² mol · L⁻¹) and its validity is found to depend strongly of the value of K. On the other hand, the relaxed NQE approximation of Fischer and Fukuda, k_c[P][N] = k_d[P N]₀ was found to be remarkably good up to values of K around 10⁻⁸ mol · L⁻¹. This upper bound is numerically found to be 2–3 orders of magnitude smaller than the theoretical one given by Fischer. The relaxed NQE is a better one due to the fact that it never completely neglects dN/dt. It is found that the difference between these approximations lies essentially in the number of significant figures taken for the approximation; still this subtle difference results in dramatic changes in the predicted course of the reaction. Some results confirm previous findings, but a deeper understanding of the physico‐chemical phenomena and their mathematical representation and another viewpoint of the theory is offered. Additionally, experiments and simulations indicate that polymerization rate data alone are not reliable to estimate the value of K, as recently suggested.

Validity of the rigorous nitroxide quasi‐equilibrium assumption as a function of the nitroxide equilibrium constant.     

Thioketone‐Mediated Polymerization of Butyl Acrylate: Controlling Free‐Radical Polymerization via a Dormant Radical Species

It is demonstrated by experiment and simulation that the commercially available thioketone 4,4‐bis(dimethylamino)thiobenzophenone is capable of controlling AIBN‐initiated bulk butyl acrylate polymerization at 80 °C. On the basis of molecular weight data and from monomer conversion versus time curves, the associated rate parameters are estimated. The addition rate coefficient, k_ad, for the reaction of a propagating chain with the thioketone is close to 10⁶ L · mol⁻¹ · s⁻¹ and the fragmentation rate coefficient, k_frag, is around 10⁻² s⁻¹ giving rise to large equilibrium constants in the order of 10⁸ L · mol⁻¹. Furthermore, cross‐ and self‐termination of the dormant radical species are identified to be operational.

     

Towards Controlled Graft Polymerization of Poly[styrene‐co‐(maleic anhydride)] on Functionalized Silica Mediated by Oxoaminium Bromide Salt. Facile Synthetic Pathway Using Nitroxide Chemistry

A TEMPO bromide salt is used to functionalize a silica surface with nitroxyl moieties. The functionalization reaction takes place in 48 h under mild conditions. In a second step, grafts of styrene‐maleic anhydride copolymer are grown from the functionalized silica surface by heating it in the presence of the monomers. FT‐IR and TGA analysis show that the silica was first functionalized with nitroxide moieties, and then that grafts of styrene‐maleic anhydride grew from the functionalized silica surface. A reaction mechanism is proposed in order to explain the findings. The results suggest that the oxoaminium salts are good candidates for the functionalization and grafting of surfaces that contain hydroxy groups and for the generation of hybrid materials with improved properties.

     

种子法制备三角形银纳米粒子及其性能表征

以十六烷基三甲基溴化胺(CTAB)为软模板剂,采用种子法制备出三角形银纳米粒子,应用透射电镜、能量散射X射线谱仪、紫外 可见分光光度计研究了粒子的性能。结果表明：所得三角形银纳米粒子是面心立方单晶,边长随着种子加入量的减少而递增,可在20～100 nm范围内调节;CTAB以薄膜形式包覆于粒子表面阻止其氧化,粒子胶体的吸收光谱呈现典型的三角形粒子吸收峰。用扫描电镜观测到粒子在硅片上自组装成一定的2维阵列结构。     

Brillouin and raman scattering studies of the melting transition in salol

Brillouin and Raman scattering studies of salol from room temperature to within 5 mK of the melting transition at T_m = 40.97°C are reported. Changes in the Brillouin shifts and linewidths were accurately determined by nonlinear least-squares fitting and deconvolution. A marked increase in the deconvoluted Brillouin linewidth (~400%) and a gradual softening (~20%) of the transverse acoustic modes were observed very close to T_m. The increase of the Brillouin linewidths was analyzed by a simple dislocation model assuming the hypersonic attenuation to be proportional to the concentration of thermally generated defects near T_m. The defect formation energy E_D(T) was computed from the temperature-dependent linewidth data, and was found to decrease significantly (~60%) near T_m, suggesting a cooperative effect producing a catastrophic growth of defects which brings about melting by destroying the long range order of the crystal. The conclusion that melting is mediated by a sudden growth of defect concentration near T_m was further strengthened by Raman scattering experiments in which 13 new Raman modes appeared close to T_m. These new modes are believed to be defect activated through breaking of the local symmetry of the crystal. A slight softening of the Raman modes (~5%) was observed close to the melting point.