A study of 1-decanethiol self-assembly on gold electrodes by computer simulation

This work is a preliminary study towards the understanding of the adsorption and self-assembly mechanisms of alkylthiols on gold electrodes. Canonical Monte Carlo simulations were performed at 298 K. The simulated model consisted of diluted solutions of 1-decanethiol in ethanol inside two gold electrodes, at the potential of zero charge. Three potentials for the oxygen–gold surface interaction were used. The liquid phase molecules were taken as rigid. The average tilt angle of the thiol molecule adsorbed on a Au(1 1 1) flat surface and the density profiles were determined. The approach of the thiol to the electrode was analyzed by calculating the variation of the Helmholtz energy along the normal to the surface. The average tilt angle is in good agreement with experimental data. Finally, we suggest possible improvements to the present model.     

生物材料纳米形貌表面对微生物细胞--荧光假单胞菌特性的影响

通过静电自组装技术在玻璃基底上组装了具备纳米尺度形貌的Al2O3和SiO2纳米粒子薄膜,并利用原子力显微镜(AFM)对两种纳米粒子薄膜的表面结构进行了表征。同时进行了荧光假单胞菌(Pseudomonasfluorescence,PF)在该纳米薄膜试片上的动态和静态黏附实验:在静态条件下研究了荧光假单胞菌黏附数在Al2O3纳米粒子薄膜片随时间的变化规律,在动态条件下对比了PF菌在纳米氧化铝、氧化硅试片、十六烷三甲基溴化铵(CTAB)和对比空白试片上黏附数、形态的不同。结果表明:静态条件下PC菌在两种试片上的黏附量皆随时间增加,PF菌在纳米粒子改性后的试片上的黏附量较之空白试片增多,而动态条件下PF菌在两种纳米粒子改性片上的形态更多的以群落(Clusters)形式出现,同时PF菌在Al2O3纳米粒子薄膜片上的黏附量大于SiO2试片。     

Hydrolysable core-crosslinked thermosensitive polymeric micelles: synthesis, characterisation and in vivo studies

In this study, core-crosslinked (CCL) biodegradable thermosensitive micelles based on mPEG₅₀₀₀ and N-(2-hydroxyethyl)methacrylamide)-oligolactates (mPEG-b-p(HEMAm-Lac_n)) were synthesised and their properties investigated. Rapidly heating aqueous solutions of partially methacrylated block copolymers to above their critical micelle temperature (CMT), followed by illumination in presence of a photoinitiator yielded almost monodisperse CCL micelles with a size of 68±7 nm. Either below the CMT or after addition of sodium dodecyl sulphate, the non-crosslinked (NCL) micelles rapidly disintegrated whereas the CCL micelles kept their integrity. NCL micelles fell apart after 5 h in pH 7.4 at 37 °C as a result of the hydrolysis of lactate side chains, whereas the CCL micelles had a much higher stability and only degraded after cleavage of the ester bonds in the crosslinks. The circulation kinetics and biodistribution of CCL micelles were considerably better than those of NCL micelles, i.e., 58% of the injected dose (ID) of CCL versus 6% of NCL micelles was recovered in the circulation 4 h post-injection. Furthermore, the liver uptake of the CCL micelles (10% ID) was much lower than that of the NCL micelles (24% ID) 4 h after administration, while tumour accumulation was almost 6 times higher for the CCL micelles. Likely, NCL micelles dissociated after i.v. administration and/or were opsonised and captured by macrophages while the dense PEG shell of CCL micelles made them less prone towards opsonisation. The excellent physical stability of these degradable CCL micelles and very favourable biodistribution profile renders them very suitable for drug targeting purposes.     

Click conjugated polymeric immuno-nanoparticles for targeted siRNA and antisense oligonucleotide delivery

Efficient and targeted cellular delivery of small interfering RNAs (siRNAs) and antisense oligonucleotides (AONs) is a major challenge facing oligonucleotide-based therapeutics. The majority of current delivery strategies employ either conjugated ligands or oligonucleotide encapsulation within delivery vehicles to facilitate cellular uptake. Chemical modification of the oligonucleotides (ONs) can improve potency and duration of activity, usually as a result of improved nuclease resistance. Here we take advantage of innovations in both polymeric delivery vehicles and ON stabilization to achieve receptor-mediated targeted delivery of siRNAs or AONs for gene silencing. Polymeric nanoparticles comprised of poly(lactide-co-2-methyl, 2-carboxytrimethylene carbonate)-g-polyethylene glycol-furan/azide are click-modified with both anti-HER2 antibodies and nucleic acids on the exterior PEG corona. Phosphorothioate (PS), 2′F-ANA, and 2′F-RNA backbone chemical modifications improve siRNA and AON potency and duration of activity. Importantly, delivery of these nucleic acids on the exterior of the polymeric immuno-nanoparticles are as efficient in gene silencing as lipofectamine transfection without the associated potential toxicity of the latter.     

Polylactide-poly(ethylene Glycol) Micellar-like Particles as Potential Drug Carriers: Production,Colloidal Properties and Biological Performance

The micellar-like particle systems produced from poly-D,L-lactide-poly(ethylene glycol) (PLA-PEG) copolymers have been assessed using a range of physicochemical characterisation methods, followed by in vivo studies of their biodistribution after intravenous administration to the rat. The size of the PEG chain was kept constant at 5 or 2 kDa, while the PLA size increased within a series from 2 to 25 kDa. The results obtained reveal, that in an aqueous medium the copolymers assembled into micellar-like structures, with the PLA segments forming the core and the PEG segments the surrounding corona. The size of the PLA segments dominated the process of assembly of the molecules and the characteristics of the resultant micellar-like particles. The PLA-PEG micellar particles were found to be less dynamic than those obtained from conventional surfactants. Particles formed from the lower molecular weight PLA polymers allowed a level of chain mobility while the cores of the micellar particles formed from higher molecular weight PLA appeared to be solid-like in nature. The size of the micellar particles was dependent on the copolymer molecular weight and the z-average diameter increased from 25 to 76 nm as the molecular weight of the PLA moiety increased. This provides an ability to control the particle size by adjusting the molecular weight of the PLA moiety. Following intravenous administration to the rat model, micellar-like particles smaller than approximately 70 nm accumulated in the liver, despite the fact that the PEG corona provided an effective steric stabilization effect. Micellar-like particles with a diameter of more than approximately 70 nm exhibited prolonged systemic circulation and reduced liver uptake, although the steric stabilisation of these particles was shown to be less effective. These findings agree with recent observations from other research groups; that indicate a possibility that very small particulates can pass through the sinusoidal fenestrations in the liver and gain access to the parenchymal cells of the liver.     

Pure photosensitizer-driven nanoassembly with core-matched PEGylation for imaging-guided photodynamic therapy

Pure drug-assembled nanomedicines (PDANs) are currently under intensive investigation as promising nanoplatforms for cancer therapy. However, poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation. Herein, we report a core-matched nanoassembly of pyropheophorbide a (PPa) for photodynamic therapy (PDT). Pure PPa molecules are found to self-assemble into nanoparticles (NPs), and an amphiphilic PEG polymer (PPa-PEG_2K) is utilized to achieve core-matched PEGylating modification via the π‒π stacking effect and hydrophobic interaction between the PPa core and the PPa-PEG_2K shell. Compared to PCL-PEG_2K with similar molecular weight, PPa-PEG_2K significantly increases the stability, prolongs the systemic circulation and improves the tumor-homing ability and ROS generation efficiency of PPa-nanoassembly. As a result, PPa/PPa-PEG_2K NPs exert potent antitumor activity in a 4T1 breast tumor-bearing BALB/c mouse xenograft model. Together, such a core-matched nanoassembly of pure photosensitizer provides a new strategy for the development of imaging-guided theragnostic nanomedicines.     

钛植入体表面生物化学改性的研究进展

综述近年来钛植入体表面生物化学设计和改性的研究进展,重点介绍植入体表面自组装改性新技术及其在生物医用材料中的应用。     

Measurement of antibodies to collagen II by inhibition of collagen fibril formation in vitro

Antibodies to type II collagen (collagen II) are pathogenic in experimental collagen-induced arthritis (CIA) and possibly also in rheumatoid arthritis (RA). Hitherto, results of assays for anti-collagen II have proven to be inconsistent. We tested whether mouse monoclonal antibodies (mAbs) to collagen II inhibit the natural self-assembly of soluble triple-stranded collagen II monomers to form insoluble polymeric fibrils. A spectrophotometric assay of self-assembly was based on change in absorbance at 313 nm, observed over 0-60 min after neutralisation and warming of a solution of monomeric collagen II. Two mAbs to collagen II (CII-CI and M2.139) strongly inhibited self-assembly of collagen II but not collagen I, whereas another antibody, CII-F4, and an irrelevant control mAb did not. Notably, CII-CI and M2.139, but not CII-F4, induce arthritis on passive transfer to na?ve mice. The arthritogenic effects of mAbs CII-CI and M2.139 in vivo, and inhibition of collagen II self-assembly in vitro, may be attributable to interference with critical epitopes at sites essential for the stabilisation of the mature polymeric collagen II fibril, and, hence, the integrity of the entire cartilage matrix. This assay for inhibition of self-assembly of collagen II could be developed for routine measurement of anti-collagen II in body fluids as a marker of early RA, and perhaps also to distinguish populations of antibodies to collagen II that either have or lack the capacity to perpetuate arthritis.     

The application of nanofibrous scaffolds in neural tissue engineering

The repairing process in the nervous system is complicated and brings great challenges to researchers. Tissue engineering scaffolds provide an alternative approach for neural regeneration. Sub-micron and nano-scale fibrous scaffolds which mimic the topography of natural extracellular matrix (ECM) can be potential scaffold candidates for neural tissue engineering. Two fiber-fabrication methods have been explored in the field of nerve regeneration: electrospinning and self-assembly. Electrospinning produces fibers with diameters ranging from several micrometers to hundreds of nanometers. The fibrous nerve conduits can be introduced at lesion sites by implantation. Self-assembly fibers have diameters of tens of nanometers and can be injected for central nervous system (CNS) injury repair. Both fibrous scaffolds would enhance neurite extension and axon regrowth. These functional nanofibrous scaffolds can serve as powerful tools for neural tissue engineering.     

Self-assembled polymeric nanoparticles of poly(ethylene glycol) grafted pullulan acetate as a novel drug carrier

Self-assembling nanospheres of hydrophobized pullulan have been developed. Pullulan acetate (PA), as hydrophobized pullulan, was synthesized by acetylation. Carboxymethylated poly(ethylene-glycol) (CMPEG) was introduced into pullulan acetate (PA) through a coupling reaction using N,N'-dicyclohexyl carbodiimide (DCC). A synthesized PA-PEG-PA (abbreviated as PEP) conjugate was confirmed by Fourier transform-infrared (FT-IR) spectroscopy. Since PEP conjugates have amphiphilic characteristics in aqueous solution, polymeric nanoparticles of PEP conjugates were prepared using a simple dialysis method in water. From the analysis of fluorescence excitation spectra primarily, the critical association concentration (CAC) of this conjugate was found to be 0.0063 g/L. Observations by scanning electron microscopy (SEM) showed the spherical morphologies of the PEP nanoparticles. The particle size distribution of the PEP conjugates was determined using photon correlation spectroscopy (PCS) and the intensity-average particle size was 193.3 +/- 13.53 nm with a unimodal distribution. Clonazepam (CNZ), as a model drug, was easy to entrap into polymeric nanoparticles of the PEP conjugates. The drug release behavior was mainly diffusion controlled from the core portion.