Development of transferrin functionalized poly(ethylene glycol)/poly(lactic acid) amphiphilic block copolymeric micelles as a potential delivery system targeting brain glioma

The aim of present study is to conceive a biodegradable poly(ethylene glycol)–polylactide (PEG–PLA) copolymer nanoparticle which can be surface biofunctionalized with ligands via biotin–avidin interactions and used as a potential drug delivery carrier targeting to brain glioma in vivo. For this aim, a new method was employed to synthesize biotinylated PEG–PLA copolymers, i.e., esterification of PEG with biotinyl chloride followed by copolymerization of hetero-biotinylated PEG with lactide. PEG–PLA nanoparticles bearing biotin groups on surface were prepared by nanoprecipitation technique and the functional protein transferrin (Tf) were coupled to the nanoparticles by taking advantage of the strong biotin–avidin complex formation. The flow cytometer measurement demonstrated the targeting ability of the nanoparticles to tumor cells in vitro, and the fluorescence microscopy observation of brain sections from C6 glioma tumor-bearing rat model gave the intuitive proof that Tf functionalized PEG–PLA nanoparticles could penetrate into tumor in vivo.     

Assembly and degradation of low-fouling click-functionalized poly(ethylene glycol)-based multilayer films and capsules

Nano-/micrometer-scaled films and capsules made of low-fouling materials such as poly(ethylene glycol) (PEG) are of interest for drug delivery and tissue engineering applications. Herein, the assembly and degradation of low-fouling, alkyne-functionalized PEG (PEG(Alk) ) multilayer films and capsules, which are prepared by combining layer-by-layer (LbL) assembly and click chemistry, are reported. A nonlinear, temperature-responsive PEG(Alk) is synthesized, and is then used to form hydrogen-bonded multilayers with poly(methacrylic acid) (PMA) at pH 5. The thermoresponsive behavior of PEG(Alk) is exploited to tailor film buildup by adjusting the assembly conditions. Using alkyne-azide click chemistry, PEG(Alk)/PMA multilayers are crosslinked with a bisazide linker that contains a disulfide bond, rendering these films and capsules redox-responsive. At pH 7, by disrupting the hydrogen bonding between the polymers, PEG(Alk) LbL films and PEG(Alk) -based capsules are obtained. These films exhibit specific deconstruction properties under simulated intracellular reducing conditions, but remain stable at physiological pH, suggesting potential applications in controlled drug release. The low-fouling properties of the PEG films are confirmed by incubation with human serum and a blood clot. Additionally, these capsules showed negligible toxicity to human cells.     

两亲嵌段共聚物的合成及纳米自组装

首先用苄氧羰基赖氨酸和三光气反应合成苄氧羰基赖氨酸酸酐,然后将聚乙二醇中活性较弱的羟基转化为氨基,最后以双端氨基聚乙二醇作为引发剂,采用阴离子开环聚合合成了聚(Nε-苄氧羰基赖氨酸)-聚乙二醇-聚(Nε-苄氧羰基赖氨酸)(PLL(Z)-PEG-PLL(Z))。PLL(Z)-PEG-PLL(Z)经去保护后得到带正电荷的聚赖氨酸-聚乙二醇-聚赖氨酸(PLL-PEG-PLL)。PLL(Z)-PEG-PLL(Z)在水溶液中自组装形成的聚集体类似于纳米多孔聚集体结构,具有疏松的空洞,原子力显微镜观测其呈球形,其大小为220 nm左右。     

Template-free synthesis of alpha-Fe2O3 hollow spindles

Alpha-Fe2O3 hollow spindles was synthesized via a one-step hydrothermal treatment via a poly(ethylene glycol) (PEG)-precursor route. Through controlling temperature, reaction time and the concentration of NaOH, we could get sphere, cubic, solid spindle and hollow spindle-like alpha-Fe2O3. The samples were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), and vibrating sample magnetometer (VSM). The magnetic research shows, the shape of the alpha-Fe2O3 nanostructure is important to their magnetic property. When the novel hollow spindle-like alpha-Fe2O3 was used as the photocatalytic material, they performed better than the solid structures.     

聚乙二醇法在温和条件下制备不同结构的磁性Fe3O4纳米晶

以Fe（acac）3为原料,乙二醇、聚乙二醇1000和聚乙二醇5000为还原剂和溶剂,在温和的溶剂热的条件下制备了不同尺寸的顺磁性Fe3O4纳米颗粒.利用X射线衍射（XRD）、光电子能谱（XPS）、透射电子显微镜（TEM）和磁性测量技术对制备的Fe3O4纳米颗粒的结构、形貌、磁性能进行了表征测试.结果发现,聚乙二醇分子链的长度对Fe3O4纳米颗粒的平均粒径大小、结晶度和饱和磁化强度均有重要影响.以乙二醇、聚乙二醇1000和聚乙二醇5000为还原剂制备的Fe3O4纳米颗粒的尺寸分别为2～3nm、5nm和7～8nm;相应的纳米Fe3O4颗粒饱和磁化强度分别为55.2、61.5和81.3emu/g;同时结晶度也随分子链的增加而增加.随分子链长度的增加,还原剂还原性的逐渐增加是导致Fe3O4纳米颗粒平均粒径大小、结晶度和饱和磁化强度逐渐增大的重要因素.     

Hollow Carbon Nanospheres with Tunable Hierarchical Pores for Drug,Gene, and Photothermal Synergistic Treatment

Design and synthesis of porous and hollow carbon spheres have attracted considerable interest in the past decade due to their superior physicochemical properties and widespread applications. However, it is still a big challenge to achieve controllable synthesis of hollow carbon nanospheres with center‐radial large mesopores in the shells and inner surface roughness. Herein, porous hollow carbon nanospheres (PHCNs) are successfully synthesized with tunable center‐radial mesopore channels in the shells and crater‐like inner surfaces by employing dendrimer‐like mesoporous silica nanospheres (DMSNs) as hard templates. Compared with conventional mesoporous nanospheres, DMSN templates not only result in the formation of center‐radial large mesopores in the shells, but also produce a crater‐like inner surface. PHCNs can be tuned from open center‐radial mesoporous shells to relatively closed microporous shells. After functionalization with polyethyleneimine (PEI) and poly(ethylene glycol) (PEG), PHCNs not only have negligible cytotoxicity, excellent photothermal property, and high coloading capacity of 482 µg of doxorubicin and 44 µg of siRNA per mg, but can also efficiently deliver these substances into cells, thus displaying enhanced cancer cell killing capacity by triple‐combination therapy.     

Preparation and characterization of hollow Fe3O4/SiO2@PEG–PLA nanoparticles for drug delivery

In this study we present a novel targeted anticancer drug delivery, which was size controlled Fe₃O₄/SiO₂ hollow microspheres (HMS) as magnetic core and poly (ethylene glycol)-poly–(d,l-lactide) (PEG–PLA) surface coating (HMS@PEG–PLA). And investigations were to test a new convenient method, which is one-step precipitation polymerization on HMS, forming magnetic hollow polymer microspheres. The HMS@PEG–PLA which have hollow structure and uniform size were characterized by Transmission Electron Microscopy (TEM). Vibrating Sample Magnetometer (VSM) showed a characteristic of super paramagnetic with saturation magnetization value of about 19.78 emu/g. In vitro cytotoxicity of Fe₃O₄/SiO₂@PEG–PLA (HMS@PEG–PLA) hollow microspheres were of low toxicity, so it can be used as a drug carrier, and cisplatin (CDDP) as the model drug release behavior was researched. The results have exhibited preferable release properties.     

Surface modification of natural rubber latex films via grafting of poly(ethylene glycol) for reduction in protein adsorption and platelet adhesion

Natural rubber (NR) latex films with surface grafted poly(ethylene glycol) (PEG) chains were prepared by UV-induced graft copolymerization of methoxy poly(ethylene glycol) monomethacrylate (PEGMA) onto the plasma-pretreated NR latex films. PEGMA macromononers of different molecular weights were used. The UV-induced graft copolymerization of PEGMA onto the plasma-pretreated NR latex films was also explored with PEGMA of different macromonomer concentrations and with different UV graft copolymerization time. The surface microstructures and compositions of the PEG-modified NR latex films were characterized by contact angle, X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM) measurements. In general, higher macromonomer concentration and longer UV graft copolymerization time led to a higher graft yield. Water contact angle measurements revealed that the hydrophilicity of the NR latex film surface was greatly enhanced by the grafting of the PEG chains. The NR surface with a high density of grafted PEG was very effective in reducing protein adsorption and platelet adhesion. A lower graft concentration of the high-molecular-weight PEG was more effective than a high graft concentration of the low-molecular-weight PEG in reducing protein adsorption and platelet adhesion. © 2001 Kluwer Academic Publishers     

Facile synthesis of magnesium oxide nanoplates via chemical precipitation

Magnesium oxide (MgO) nanoplates, which have a thickness of about 10–20 nm and a length of up to 100 nm, are synthesized via chemical precipitation using ammonia hydroxide as precipitator in the presence of a nonionic surfactant polyethylene glycol (PEG 400). The morphologies and structures of the synthesized nanoplates have been characterized by transmission electron microscopy (TEM) and X-ray diffraction (XRD). Furthermore, the mechanism for the formation of the nanoplates has been preliminarily discussed. It is believed that the capping molecule of PEG 400, which inhibits crystal growth along the (001) direction due to its selective adsorption, plays a critical role in the formation of the plate-like nanostructures.     

Synthesis and layer-by-layer self-assembly of silver nanoparticles capped by mercaptosulfonic acid

Spherical silver nanoparticles capped by mercaptosulfonic acid with a diameter of about 8 nm were prepared by a simple chemical reaction. The resulting silver nanoparticles were characterized by UV–vis spectroscopy (UV–vis) and transmission electron microscopy (TEM). Using layer-by-layer (LBL) self-assembly technique, the multilayer films containing silver nanoparticles and polycation poly(dialyldimethylammonium chloride) (PDDA) were successfully fabricated. The fabrication process was monitored by UV–vis spectra and the morphology of the multilayer films was investigated by atomic force microscopy (AFM). The cyclic voltammogram (CV) measurements further confirmed that the silver nanoparticles had assembled into the multilayer films successfully. Surface-enhanced Raman spectroscopy (SERS) measurements showed that the multilayer films containing silver nanoparticles could serve as SERS-active substrate.     

DNA multilayer films on planar and colloidal supports: sequential assembly of like-charged polyelectrolytes

Multilayer films comprising solely negatively charged polyelectrolytes were sequentially assembled based on DNA hybridization. Films prepared from alternating layers of two-block homopolymeric nucleotides (polyA(20)G(20)/polyT(20)C(20)) grew linearly with increasing layer number, as verified by quartz crystal microgravimetry, UV-vis spectrophotometry and optical microscopy. Urea treatment of the films induced morphological changes, while exposure to low ionic strength solutions resulted in film disassembly. DNA multilayer films were also formed on silica particles, and DNA hollow capsules were obtained following dissolution of the template core.     

纳米银颗粒的制备及其影响因素研究

以硝酸银为银源,利用超声化学法,加入稳定荆聚乙二醇400,制备出纳米银颗粒。分别用银铵络合离子法、有机溶剂法制备纳米银粒子,并进行了对比分析。通过透射电子显微镜观察纳米银的粒径大小及形貌,利用能谱、X射线衍射和紫外-可见分光光度计对纳米银进行了表征,并讨论了不同的反应温度、超声时间、溶剂种类以及不同稳定剂浓度对纳米银颗粒的形成及粒径的影响。     

A focus on the features of polyaniline nanofibres prepared via developing the single crystals of their block copolymers with poly(ethylene glycol)

Poly(ethylene glycol) (PEG)–polyaniline (PANI) diblock and triblock copolymers were synthesized via copolymerization of aniline with amine-terminated PEG by interfacial polymerization using sulphuric acid as dopant and ammonium peroxydisulfate (APS) as well as potassium hydrogen diiodate (PHD) as oxidants. The PHD-based synthesized PANI nanorods possessed longer lengths, narrower diameter distribution and higher conductivity. The electroactivity of synthesized copolymers was characterized using ultraviolet–visible (UV–Vis) spectrometry, cyclic voltammetry (CV) and resistivity measurement. Even in the presence of dielectric PEG blocks, the synthesized block copolymers had a conductivity around 3 S \(\hbox {cm}^{-1}\). In a further step, the solution-grown single crystals were prepared to investigate the general features of grafted PANI nanorods using small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM) and atomic force microscopy (AFM). Based on AFM and SAXS analyses, the bimodal gel permeation chromatography (GPC) traces obtained from the block copolymers were originated from the diameter distribution of nanofibres, not from the dispersity of their lengths and molecular weights.     

Enhanced dispersity of gold nanoparticles modified by omega-carboxyl alkanethiols under the impact of poly(ethylene glycol)s

The physisorption of nonionic surfactant poly(ethylene glycol) (PEG) series and the chemisorption of carboxyl-terminated alkanethiols on surface of gold nanoparticles (AuNPs) were investigated. The physical adsorption of oligo(ethylene glycol) moieties introduced a tiny red shift of surface plasmon resonance (SPR) of AuNPs, indicating the formation of a protective layer of PEG molecules around gold surface. The subsequent chemisorption of omega-carboxyl alkanethiols was performed under the protection of PEG molecules, and the aggregation of metal nanoparticles did not appear by TEM observation. The successful adsorption of omega-carboxyl alkanethiol on gold surface was demonstrated according to FT-IR spectrum and the prior adsorbed PEG molecules could be washed out by centrifugation. Furthermore, the presence of nonionic surfactant even displayed a protective role in centrifugal process. The dispersity of modified AuNPs with peripheral functional groups was enhanced under the protection of PEG molecules as an important advantage in further biological applications.     

Surface modification of poly(ethylene terephthalate) by plasma polymerization of poly(ethylene glycol)

Poly(ethylene glycol) (PEG) was ‘polymerized’ onto poly(ethylene terephthalate) (PET) surface by radio frequency (RF) plasma polymerization of PEG (average molecular weight 200 Da) at a monomer vapour partial pressure of 10 Pa. Thin films strongly adherent onto PET could be produced by this method. The modified surface was characterized by infra red (IR) spectroscopy, scanning electron microscopy (SEM), atomic force microscopy (AFM), cross-cut test, contact angle measurements and static platelet adhesion studies. The modified surface, believed to be extensively cross-linked, however showed all the chemical characteristics of PEG. The surface was found to be highly hydrophilic as evidenced by an interfacial free energy of about 0.7 dynes/cm. AFM studies showed that the surface of the modified PET became smooth by the plasma polymerized deposition. Static platelet adhesion studies using platelet rich plasma (PRP) showed considerably reduced adhesion of platelets onto the modified surface by SEM. Plasma ‘polymerization’ of a polymer such as PEG onto substrates may be a novel and interesting strategy to prepare PEG-like surfaces on a variety of substrates since the technique allows the formation of thin, pin-hole free, strongly adherent films on a variety of substrates.     

Synthesis of poly(ethylene glycol) functionalized MWNTs and their inclusion complexes with α-cyclodextrin

Poly(ethylene glycol) (PEG) functionalized multiwalled carbon nanotubes (MWNTs), prepared by coupling of isocyanate-decorated MWNTs with PEG of different molecular weights (M _n = 400, 1000, 2000, and 4000 g/mol), were used to form inclusion complexes (ICs) with α-cyclodextrin (α-CD) through the grafted PEG chains being threaded with α-CD rings in aqueous solution. The FTIR, TGA, UV-Vis, and scanning electron microscopy (SEM) techniques were employed to characterize the formed ICs. The ICs formation time was monitored by UV-Vis spectroscopy, and the results indicated that the inclusion interaction between MWNT surface anchored PEG chains and α-CD was dependent on the molecular weight of PEG. The grafted PEG with molecular weights of 4000 and 2000 g/mol, respectively, can form ICs with α-CD, while the grafted PEG with molecular weights of 1000 and 400 g/mol, respectively, are difficult to form ICs with α-CD due to the steric hindrance from nanotubes. The stoichiometry value determined by TGA indicated that the ratio of ethylene glycol (EG) unit to α-CD in the resulted ICs was about 15:1. In addition, the morphology of the ICs was observed by SEM and transmission electron microscopy (TEM).     

两亲性PS-b-PEG-b-PS三嵌段共聚物的合成及在水中的聚集行为研究

采用原子转移自由基(ATRP)合成了一系列两端为短的聚苯乙烯(PS)嵌段,中间为长的聚乙二醇(PEG)嵌段的PS-b-PEG-b-PS两亲性三嵌段共聚物。采用1H-NMR、荧光探针法和动态光散射研究了PS和PEG嵌段长度对三嵌段共聚物在水中聚集行为的影响。结果表明:三嵌段共聚物在水中可以形成以PS嵌段为核和以PEG嵌段为壳的球形胶束,其胶束化的临界胶束浓度(CMC)随着PS嵌段长度增加而减小,流体力学半径(Rh)随PEG嵌段长度增长而增大,调整PS嵌段长度能有效地调控胶束的形成。胶束对疏水分子芘具有很好的装载能力,芘在胶束中的分配平衡常数(Kv)为105,随PS嵌段长度增加而增大。     

Poly(ethylene glycol) decorated poly(methylmethacrylate) nanoparticles for protein adsorption

Poly(ethylene glycol) decorated poly(methyl methacrylate) particles were synthesized by means of emulsion polymerization using poly(ethylene glycol) sorbitan monolaurate (Tween-20) as surfactant. PMMA/PEG particles presented mean diameter (195 ± 15) nm, indicating narrow size distribution. The adsorption behavior of bovine serum albumin (BSA) and concanavalin A (ConA) onto PMMA/PEG particles was investigated by means of spectrophotometry. Adsorption isotherms obtained for BSA onto PMMA/PEG particles fitted well sigmoidal function, which is typical for multilayer adsorption. Con A adsorbed irreversibly onto PMMA/PEG particles. The efficiency of ConA covered particles to induce dengue virus quick agglutination was evaluated.     

Preparation of aluminum–organic nanocomposite materials via wet chemical process

Aluminum–organic composite nanoparticles were synthesized by a modified Haber and Buhro’s process; ethylene glycol (EG) was used as solvent instead of 1,2,3-trimethyl benzene. The use of EG caused an extremely active reaction in the preparation of aluminum nanoparticles, and the subsequent polymerization of EG to produce polyethylene glycol (PEG) occurred on the prepared aluminum nanoparticle surface due to the active reaction. Carboxylic agent passivation on the surface of the prepared Al–PEG particles was successfully performed, and TEM and FT-IR analyses clearly showed that the resulting prepared particles, which had a geometric mean diameter of ～55 nm, consisted of an aluminum core and PEG and oleic acid layers. As result of a floating test performed for seven days, the resulting prepared Al–PEG–oleic acid composite nanoparticles showed good properties in the inhibition of oxidation and humidity absorption.     

Production of free standing composite membranes or of patterned films after sol–gel reactions in an exponential layer-by-layer architecture

This paper aims at describing that polyelectrolyte multilayer (PEM) films, made of biocompatible molecules, Hyaluronic acid (HA) and Poly(6-lysine) (PLL), can entrap negatively charged precursors of titania or silica. These precursors undergo hydrolysis and polycondensation in contact with the amino groups of PLL leading to the formation of oxides (TiO₂ or SiO₂) within the films. Moreover, this work shows that these composite thin films, a few μm thick, can be easily detached as free standing membranes containing photoactive TiO₂. To this aim the PEM film containing TiO₂ was thermally cross-linked to form amide bonds. Immersion of the film in diluted hydrofluoric acid (2% (v/v)) allowed then the formation of a free standing membrane. We extend the concept of sol–gel reaction in PEM films to films made from poly(L-glutamic acid) (PGA) and Poly(allylamine) (PAH) and show that the composition of the multilayer film influences the distribution of the inorganic material in the films: the TiO₂ distribution seems homogeneous in (PLL–HA)_n films whereas the (PAH–PGA)_n films are self patterned with inorganic aggregates tens of micrometers in diameter. The free standing membranes or self patterned composite films obtained in this investigation may present interesting bio-applications.