壳聚糖/乙酰半胱氨酸纳米粒子的性质及体外释药性

制备了一种基于壳聚糖/乙酰半胱氨酸偶合物(CS-NAC)的新型巯基纳米粒子并进行了结构表征, 同时对纳米粒子的黏附性、溶胀性和药物释放进行了测试. 结果表明, 纳米粒子具有较小的粒径(140~210 nm)和正的表面电位(19.5~31.7 mV), 胰岛素的载药量达到13%~42%. 这些性质随着巯基含量的变化而变化. 与壳聚糖纳米粒子相比, 巯基壳聚糖纳米粒子表现出了更强更快的黏附性质. 体外释放研究结果表明, 巯基壳聚糖纳米粒子的胰岛素释放具有pH响应性. 在pH=6.8时, 15 min即能释放58.6 %的胰岛素; 而在pH=5.4时, 24 h内仅有不到40%的胰岛素被释放. 因此, CS-NAC纳米粒子用于胰岛素的黏膜给药体系具有很好的应用前景.     

Impact of Polycyclic Aromatic Hydrocarbons on the Electrochemical Responses of a Ferricyanide Probe at Template‐Modified Self‐Assembled Monolayers on Gold Electrodes

The impact of polycyclic aromatic hydrocarbons (PAHs) on the electrochemical responses of a ferricyanide probe using gold electrodes coated with template‐containing self‐assembled monolayers (SAMs) was investigated using cyclic voltammetry and square‐wave voltammetry. The thiolated compounds that were used to form SAMs included 1‐hexadecanethiol, 11‐mercapto‐undecanoic acid, 11‐mercaptoundecanol, and (3‐mercaptopropyl) trimethoxysilane (MPTS). When the SAMs were formed from 1‐hexadecanethiol or 11‐mercapto‐undecanoic acid in the absence of pyrene, the SAM‐modified electrodes prohibited access of the ferricyanide probe and no impact of pyrene was observed. SAM‐modified electrodes (all except for MPTS) that were formed in the presence of pyrene then washed free of pyrene showed an increase in accessibility of the probe ferricyanide upon the addition of pyrene to the electrolyte solution. When electrodes were modified with MPTS to form stabilized SAMs in the presence of pyrene, however, a reduced redox current for the ferricyanide probe was observed with increased pyrene or naphthalene in the electrolyte solution. A degree of selectivity was noted in that this current response was not observed for addition of benzo[a]pyrene.     

Application of thiolated gold nanoparticles for the enhancement of glucose oxidase activity

Glucose oxidase (GOx) has been covalently immobilized onto chemically synthesized thiolated gold nanoparticles (5-8 nm) via N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The lower value of the Michaelis-Menton constant obtained for the immobilized (3.74 mM) GOx compared with that for the free (5.85 mM) GOx suggests significant enhancement in the activity of GOx attached to thiolated gold nanoparticles. The covalently immobilized GOx thiolated nanoparticles exhibit a response time of 30 s, a shelf life of more than 6 months, and improved tolerance to both pH and temperature.     

Diamond nanoparticles as a way to improve electron transfer in sol–gel l-lactate biosensing platforms

In the present work, we have included for the first time diamond nanoparticles (DNPs) in a sol–gel matrix derived from (3-mercaptopropyl)-trimethoxysilane (MPTS) in order to improve electron transfer in a lactate oxidase (LOx) based electrochemical biosensing platform. Firstly, an exhaustive AFM study, including topographical, surface potential (KFM) and capacitance gradient (CG) measurements, of each step involved in the biosensing platform development was performed. The platform is based on gold electrodes (Au) modified with the sol–gel matrix (Au/MPTS) in which diamond nanoparticles (Au/MPTS/DNPs) and lactate oxidase (Au/MPTS/DNPs/LOx) have been included. For the sake of comparison, we have also characterized a gold electrode directly modified with DNPs (Au/DNPs). Secondly, the electrochemical behavior of a redox mediator (hydroxymethyl-ferrocene, HMF) was evaluated at the platforms mentioned above. The response of Au/MPTS/DNPs/LOx towards lactate was obtained. A linear concentration range from 0.053 mM to 1.6 mM, a sensitivity of 2.6 μA mM⁻¹ and a detection limit of 16 μM were obtained. These analytical properties are comparable to other biosensors, presenting also as advantages that DNPs are inexpensive, environment-friendly and easy-handled nanomaterials. Finally, the developed biosensor was applied for lactate determination in wine samples.     

Mesoporous silica materials with an extremely high content of organic sulfonic groups and their comparable activities with that of concentrated sulfuric acid in catalytic esterification

Mesoporous silica materials (HS-JLU-20) with an extremely high content of mercaptopropyl groups have been successfully synthesized using fluorocarbon-hydrocarbon surfactant mixtures through a simple co-condensation approach of tetraethyl orthosilicate (TEOS) and (3-mercaptopropyl)trimethoxysilane (MPTS), which are characterized by X-ray diffraction (XRD), nitrogen adsorption and desorption isotherms, transmission electron microscopy (TEM), CHNS elemental analysis, thermogravimetry analysis (TGA), and (29)Si NMR spectroscopy. The results show that HS-JLU-20 samples with molar ratios of MPTS/(MPTS + TEOS) at 0.5-0.8 in the starting synthetic gels still show their mesostructures, while HS-SBA-15 with the molar ratio of MPTS/(MPTS + TEOS) at 0.50 completely loses its mesostructure in the absence of fluorocarbon surfactant. Possibly, fluorocarbon surfactant containing N(+) species with a positive charge could effectively interact with negatively charged mercapto groups in the synthesis of HS-JLU-20 materials, resulting in the formation of mesoporous silicas with good cross-linking of silica condensation even at an extremely high content of organic mercapto groups. More interestingly, after the treatment with hydrogen peroxide, HSO(3)-JLU-20 materials with an extremely high content of organic sulfonic groups exhibit comparable activity with liquid concentrated sulfuric acid in catalytic esterification of cyclohexanol with acetic acid.     

Thiolated PAMAM dendrimer-coated CdSe/ZnSe nanoparticles as protein transfection agents

Functionalisation of PAMAM dendrimers with a small number of thiol groups makes them good ligands for CdSe/ZnSe nanoparticles; the particles coated with thiolated dendrimers have good cell permeability and are potent transfection agents.     

Hydrogen-bonding-driven self-assembly of PEGylated organosilica nanoparticles with poly(acrylic acid) in aqueous solutions and in layer-by-layer deposition at solid surfaces

PEGylated organosilica nanoparticles have been synthesized through self-condensation of (3-mercaptopropyl)trimethoxysilane in dimethyl sulfoxide into thiolated nanoparticles with their subsequent reaction with methoxypoly(ethylene glycol) maleimide. The PEGylated nanoparticles showed excellent colloidal stability over a wide range of pH in contrast to the parent thiolated nanoparticles, which have a tendency to aggregate irreversibly under acidic conditions (pH < 3.0). Due to the presence of a poly(ethylene glycol)-based corona, the PEGylated nanoparticles are capable of forming hydrogen-bonded interpolymer complexes with poly(acrylic acid) in aqueous solutions under acidic conditions, resulting in larger aggregates. The use of hydrogen-bonding interactions allows more efficient attachment of the nanoparticles to surfaces. The alternating deposition of PEGylated nanoparticles and poly(acrylic acid) on silicon wafer surfaces in a layer-by-layer fashion leads to multilayered coatings. The self-assembly of PEGylated nanoparticles with poly(acrylic acid) in aqueous solutions and at solid surfaces was compared to the behavior of linear poly(ethylene glycol). The nanoparticle system creates thicker layers than the poly(ethylene glycol), and a thicker layer is obtained on a poly(acrylic acid) surface than on a silica surface, because of the effects of hydrogen bonding. Some implications of these hydrogen-bonding-driven interactions between PEGylated nanoparticles and poly(acrylic acid) for pharmaceutical formulations are discussed.     

Programmed placement of gold nanoparticles onto a slit-type DNA origami scaffold

A novel DNA scaffold, called a DNA slit, was designed for the programmed positioning of Au nanoparticles (AuNPs), and various patterns of thiolated DNA slits were constructed. AuNPs were correctly placed at the predesigned positions in the thiolated DNA slits, indicating that the thiolated staples and the slit cavities guide the correct assembly of AuNPs.     

Asymmetric cellulose nanocrystals: thiolation of reducing end groups via NHS–EDC coupling

Cellulose nanocrystals (CNC) were functionalized in aqueous media at the reducing, aldehyde ends of cellulose. CNC oxidation to produce carboxyl groups was followed by carbodiimide-mediated reaction to install thiol groups. The selectivity and extent of thiolation at the reducing ends was qualitatively confirmed by imaging (transmission electron microscopy) silver nanoparticles that tagged the CNC termini and by X-ray photoelectron spectroscopy, respectively. The adsorption of thiolated CNC onto gold surfaces as well as the viscoelastic property of the formed adlayer was investigated by using quartz crystal microgravimetry. The thiolated CNC chemisorbed on the surfaces were further analyzed for surface density and distribution by using atomic force microscopy. Overall we introduce a facile, mild asymmetric thiolation procedure as an efficient alternative to conventional reductive amination.     

Surface functionalization of ZrO2 nanocrystallites for the integration into acrylate nanocomposite films

Surface functionalized zirconia nanoparticles were prepared by covalent grafting of a methacrylate functionalized silane (methacryloxypropyltrimethoxysilane, MPTS) onto the surface of the zirconia nanoparticles (tetragonal and mixed monoclinic/tetragonal phase) obtained by hydrothermal treatment of zirconyl chloride octahydrate. The particles are 70 nm aggregates of nanometric primary grains (4-12 nm) with inter particle porosity. BET measurements show that the specific surface area of the particles after activation at 100 degrees C is between 85 and 204 m2/g depending on the mineralizer used (Sr2+, Ca2+, Mg2+). IR-measurements show that the surface of the particles can be covered with functional groups bound through a variable number of ZrOSi bonds to render them organocompatible. The surface modified particles were dispersed in monomer solution (butanediol monoacrylate, BDMA) and polymerized to form films by adding a cross linking agent (trimethylolpropane triacrylate, Laromer TMPTA) and an UV initiator (2,4,6-trimethylbenzoyldiphenylphosphine oxide, Lucirin TPO). The received films were characterized with thermogravimetry and UV-vis spectroscopy.     

Synthesis of MPTS-modified cobalt ferrite nanoparticles and their adsorption properties in relation to Au(III)

Cobalt ferrite magnetic nanoparticles (Co-MNP) were prepared by a co-precipitation method and subsequently coated with (3-mercaptopropyl)trimethoxysilane (MPTS) for the extraction and recovery of Au(III) from aqueous chloride solutions. Physical characterization of the MPTS-modified particles (Co-MPTS) was performed using FT-IR, TGA, and SEM. Results from FT-IR confirmed that MPTS was present on the surface of the magnetic nanoparticles. The amount of MPTS was 0.36 mmol g⁻¹ of Co-MPTS, obtained by elemental analysis. SEM images revealed aggregates composed of nanocrystalline Co-MPTS particles. The extraction efficiency as a function of the pH, contact time, and initial Au(III) concentration was evaluated. The modified particles showed maximum adsorption in the pH range from 1.0 to 4.0. The adsorption behavior of Co-MPTS toward Au(III) followed a Langmuir isotherm and the maximum adsorption capacity was found to be 120.5 mg g⁻¹. The stability of the modified materials was improved as compared to that of bare Co-MNP. The subsequent desorption of gold could be achieved by using acidified thiourea solution; the highest gold recovery reached 85%.     

Dual‐Amplification of Antigen–Antibody Interactions via Backfilling Gold Nanoparticles on (3‐Mercaptopropyl) Trimethoxysilane Sol‐Gel Functionalized Interface

A new dual‐amplification strategy of electrochemical signaling from antigen–antibody interactions was proposed via backfilling gold nanoparticles on (3‐mercaptopropyl) trimethoxysilane sol‐gel (MPTS) functionalized interface. The MPTS was employed not only as a building block for the electrode surface modification but also as a matrix for ligand functionalization with first amplification. The second signal amplification strategy introduced in this study was based on the backfilling immobilization of nanogold particles to the immunosensor surface. Several coupling techniques, such as with nanogold but not MPTS or with MPTS but not nanogold, were investigated for the determination of carcinoembryonic antigen (CEA) as a model, and a very good result was obtained with nanogold and MPTS coupling immunosensor. With the noncompetitive format, the formation of the antigen–antibody complex by a simple one‐step immunoreaction between the immobilized anti‐CEA and CEA in sample solution introduced membrane potential change before and after the antigen–antibody interaction. Under optimal conditions, the proposed immunosensor exhibited a good electrochemical behavior to CEA in a dynamic concentration range of 4.4 to 85.7 ng/mL with a detection limit of 1.2 ng/mL (at 3 δ). Moreover, the precision, reproducibility and stability of the as‐prepared immunosensor were acceptable. Importantly, the proposed methodology would be valuable for diagnosis and monitoring of carcinoma and its metastasis.     

Amino‐Containing Ultrafine Organosilica‐Nanoparticle‐Modified Au Electrode for the Determination of Cu(II) Ions

Using 3‐Aminopropyltriethoxysilane(APTES) as a single silica source, an amino‐rich ultrafine organosilica‐nanoparticle‐modified Au electrode was fabricated, following the formation of (3‐mercaptopropyl)‐trimethoxysilane (MPTS) monolayer on Au surface (MPTS/Au). With cetyltrimethylammonium bromide as an additive, APTES‐based gel particles on the electrode have a narrow particle size distribution of 4–7 nm and “crystal‐like” structure. AFM and electrochemical characterization confirmed the successful grafting of APTES nanoparticles on MPTS/Au. The APTES/MPTS/Au electrode is highly sensitive for the detection of copper(II) ions with a detection limit as low as 1.6×10^?12 mol L^?1 (S/N>3) by square wave voltammetry. The current is linear to copper(II) concentration between 1.6×10^?12 and 6.25×10^?10 mol L^?1.     

表面电荷对聚乙二醇修饰金纳米粒子生物行为的影响

利用硫-金键将末端修饰甲氧基、氨基或羧基的巯基化聚乙二醇(Thiolated polyethylene glycol,HS-PEG)分子分别组装到金纳米粒子表面, 合成了3种带有不同表面电荷的聚乙二醇修饰金纳米粒子(PEGylated gold nanoparticles,PEG-Au NP).细胞共培养和小鼠尾静脉注射实验结果表明,表面电荷能够显著影响PEG-Au NP的生物行为.细胞对PEG-Au NP的吞噬量遵循正电荷＞电中性＞负电荷的规律.尾静脉注射的PEG-Au NP能够随小鼠的血液循环由全器官分布逐渐向肝脾转移.表面带负电荷的PEG-Au NP较难被小鼠肝脾清除,带但正电荷的PEG-Au NP能够引起小鼠免疫系统较强的响应.     

Synthesis of oligonucleotides carrying thiol groups using a simple reagent derived from threoninol

Oligonucleotides carrying thiol groups are useful intermediates for a remarkable number of applications involving nucleic acids. In this study, DNA oligonucleotides carrying tert-butylsulfanyl (t-BuS) protected thiol groups have been prepared. A building block derived from threoninol has been developed to introduce a thiol group at any predetemined position of an oligonucleotide. The resulting thiolated oligonucleotides have been used for the preparation of oligonucleotide conjugates and for the functionalization of gold nanoparticles using the reactivity of the thiol groups.     

A two-color-change, nanoparticle-based method for DNA detection

Herein, we describe the detailed synthesis of Ag/Au core-shell nanoparticles, the surface-functionalization of these particles with thiolated oligonucleotides, and their subsequent use as probes for DNA detection. The Ag/Au core-shell nanoparticles retain the optical properties of the silver core and are easily functionalized with thiolated oligonucleotides due to the presence of the gold shell. As such, the Ag/Au core-shell nanoparticles have optical properties different from their pure gold counterparts and provide another “color” option for target DNA-directed colorimetric detection. Size-matched Ag/Au core-shell and pure gold nanoparticles perform nearly identically in DNA detection and melting experiments, but with distinct optical signatures. Based on this observation, we report the development of a two-color-change method for the detection and simultaneous validation of single-nucleotide polymorphisms in a DNA target using Ag/Au core-shell and pure gold nanoparticle probes.     

Biofunctionalized block copolymer nanoparticles based on ring‐opening metathesis polymerization

We present an approach to the synthesis of biofunctionalized block copolymer nanoparticles based on ring‐opening metathesis polymerization; these nanoparticles may serve as novel scaffolds for the multivalent display of ligands. The nanoparticles are formed by the self‐assembly of diblock copolymers composed of a hydrophobic block and a hydrophilic activated block that can be functionalized with thiolated ligands in aqueous media. The activated block enables control over the orientation of the displayed ligands, which may be sugars, peptides, or proteins engineered to contain cysteine residues at suitable locations. The nanoparticle diameter can be varied over a wide range through changes in the composition of the block copolymer, and biofunctionalization of the nanoparticles has been demonstrated by the attachment of a peptide previously shown to inhibit the assembly of anthrax toxin. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 928–939, 2006     

Ultrafast cooling of photoexcited electrons in gold nanoparticle-thiolated DNA conjugates involves the dissociation of the gold-thiol bond

Using UV-visible extinction spectroscopy and femtosecond pump-probe transient absorption spectroscopy, we have studied the effect of femtosecond laser heating on gold nanoparticles attached to DNA ligands via thiol groups. It is found that femtosecond pulse excitation of the DNA-modified nanoparticles at a wavelength of 400 nm leads to desorption of the thiolated DNA strands from the nanoparticle surface by the dissociation of the gold-sulfur bond. The laser-initiated gold-sulfur bond-breaking process is a new pathway for nonradiative relaxation of the optically excited electrons within the DNA-modified gold nanoparticles, as manifested by a faster decay rate of the excited electronic distribution at progressively higher laser pulse energies. The experimental results favor a bond dissociation mechanism involving the coupling between the photoexcited electrons of the nanoparticles and the gold-sulfur bond vibrations over one involving the conventional phonon-phonon thermal heating processes. The latter processes have been observed previously by our group to be effective in the selective photothermal destruction of cancer cells bound to anti-epidermal growth factor receptor-conjugated gold nanoparticles.     

基于金纳米粒子掩模的硅表面纳米结构加工

利用金溶胶纳米粒子为掩模,结合轻敲模式原子力显微镜（TM AFM）的局域氧化技术和化学湿法腐蚀,对Si表面进行纳米尺度的结构加工,得到柱状和环状纳米结构.实验结果表明,氧化过程中AFM针尖与样品平均间距的大小显著影响后续纳米结构的形状.保持一定的氧化偏压、扫描速度和相对湿度,当针尖与样品间距为7.5 nm时,可得到柱状纳米结构;而当间距减小到5 nm时,则得到带芯环状纳米结构.不同几何形状的纳米结构形成的原因是体系中纳米粒子物理屏蔽效应.     

用第一原理理解与预测巯基金纳米簇

This is an exciting time for studying thiolated gold nanoclusters.Single crystal structures of Au102(SR)44 and Au25(SR) 1-8 (—SR being an organothiolate group) bring both surprises and excitement in this field.First principles density functional theory (DFT) simulations turn out to be an important tool to understand and predict thiolated gold nanoclusters.In this review,I summarize the progresses made by us and others in applying first principles DFT to thiolated gold nanoclusters,as inspired by the recent ...