Strong host-guest interaction enables facile and controllable surface modification of cucurbit[6]uril-based polymer nanocapsules for in vivo cancer targeting

Cucurbit[6]uril-based polymer nanocapsules (CB[6]PNs), covalently conjugated with a near-infrared dye (Cy 7), was exploited as a stable platform (Cy7-CB[6]PNs) for in vivo cancer targeting. The strong host-guest interaction between CB[6] and spermidine (spmd) enabled us to modify the surface of the nanocapsules with spmd-conjugated cancer targeting functional tags in a facile, controllable and non-covalent manner. Thanks to the strong host-guest interaction retained even in the bloodstream of a mouse, enhanced accumulation of Cy7-CB[6]PNs on cancer tissues of mice was successfully detected via NIR imaging when the nanocapsules were treated with more number of the cancer targeting functional tags. This result showed the potential of the CB[6]-based strong host-guest interaction as a controllable and efficient tool for surface modification of in vivo cancer targeting nanomaterials.     

不同表面官能团和化学组成共聚物微球的表面生物矿化研究

采用具有不同共聚物组成和端基官能团的聚己内酯-b-聚乙二醇共聚物(PCL-b-PEG),通过双乳液溶剂挥发法制备了一系列具有不同表面性质的生物降解高分子微球.采用生物模拟矿化的方法以磷灰石修饰微球表面.进一步通过扫描电镜、热重分析仪、X-射线衍射仪和光电子能谱仪对微球表面磷灰石的形貌、含量、结构和组成进行了分析.研究了微球表面亲水性、粗糙度、官能团以及矿化时间对于磷灰石形成的影响.最终实验结果表明,随着共聚物中PEG含量增加,微球表面粗糙度和亲水性增加,因此微球表面磷灰石含量增加.同时微球表面官能团以及矿化时间的不同也会对磷灰石的形成和分布产生明显影响.     

Scope and limitations of surface functional group quantification methods: exploratory study with poly(acrylic acid)-grafted micro- and nanoparticles

The amount of grafted poly(acrylic acid) on poly(methyl methacrylate) micro- and nanoparticles was quantified by conductometry, (13)C solid-state NMR, fluorophore labeling, a supramolecular assay based on high-affinity binding of cucurbit[7]uril, and two colorimetric assays based on toluidine blue and nickel complexation by pyrocatechol violet. The methods were thoroughly validated and compared with respect to reproducibility, sensitivity, and ease of use. The results demonstrate that only a small but constant fraction of the surface functional groups is accessible to covalent surface derivatization independently of the total number of surface functional groups, and different contributing factors are discussed that determine the number of probe molecules which can be bound to the polymer surface. The fluorophore labeling approach was modified to exclude artifacts due to fluorescence quenching, but absolute quantum yield measurements still indicate a major uncertainty in routine fluorescence-based surface group quantifications, which is directly relevant for biochemical assays and medical diagnostics. Comparison with results from protein labeling with streptavidin suggests a porous network of poly(acrylic acid) chains on the particle surface, which allows diffusion of small molecules (cutoff between 1.6 and 6.5 nm) into the network.     

Preparation of quantum dots encoded microspheres by electrospray for the detection of biomolecules

In this paper, a novel method based on the electrospray technique has been developed for preparation of quantum dot (QD)-encoded microspheres for the fist time. By electrospraying the mixture of polymer solution and quantum dots solution (single-color QDs or multi-color QDs), it is accessible to obtain a series of composite microspheres containing the functional nanoparticle. Poly(styrene-acrylate) was utilized as the electrospray polymer materials in order to obtain the microsphere modified with carboxyl group on the surface. Moreover, to test the performance of the QD-encoded microsphere in bioapplication, it is carried out that immunofluorescence analysis between antigens of mouse IgG immobilized on the functional microsphere and FITC labeled antibodies of goat-anti-mouse IgG in experiment. To the best of our knowledge, this is the first report of QD-encoded microspheres prepared by electrospray technology. This technology can carry out the one-pot preparation of different color QD-encoded microspheres with multiple intensities. This technology could be also suitable for encapsulating other optical nanocrystals and magnetic nanoparticles for obtaining multifunctional microspheres. All of the results in this paper show that the fluorescence beads made by electrospray technique can be well applied in multiplex analysis. These works provide a good foundation to accelerate application of preparing microspheres by electrospray technique in practice.     

Preparation of raspberry-like polystyrene/carbon black composite microsphere via π–π interactions

Polystyrene (PS)/carbon black (CB) composite microspheres were prepared using a modified CB, which was prepared by blending CB with a hindered phenol antioxidant Irganox 1330 in an internal mixer. Scanning electron microscopy indicated that the modified CB adsorbed on the surface of PS microspheres homogenously to form a raspberry-like morphology composite. The non-covalent binding of Irganox 1330 on the surface of PS microsphere was observed from the UV-Vis absorption spectrum in ethanol, while the fluorescence of PS was almost totally quenched by the binding of Irganox 1330. These results implied there were aromatic interactions between Irganox 1330 and the PS microspheres, which played a crucial role in the formation of composite microspheres. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Functionalization of carbon black nanoparticles with poly(vinylidene fluoride)

The surface of carbon black (CB) nanoparticles was functionalized with poly(vinylidene fluoride) (PVDF) either by trapping of macroradicals or by cycloaddition. PVDF with two iodine end groups (I‐PVDF‐I) obtained from iodine transfer polymerization in supercritical CO₂ was heated in the presence of CB and the C? I bond was cleaved resulting in a reaction between the macroradical and the CB surface. To allow for cycloaddition of PVDF to the CB surface for a number of polymers, the iodine end groups were replaced by azide end groups. In addition, microwave irradiation was applied to the functionalization. The influence of temperature, time, polymer concentration, and polymer molar mass on the functionalization reaction was examined. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

光/还原双重响应水凝胶微球的制备及在细胞三维(3D)培养中的应用

设计合成了一种光/还原双响应水凝胶微球, 该微球可在温和的刺激条件下实现三维(3D)细胞的大规模培养和无酶无损捕获. 水凝胶微球组分中包含一个双响应功能单体(M1), 其中邻硝基苄酯功能基团可在紫外光照下与氨基化合物发生光偶联作用, 从而在水凝胶微球表面实现黏附蛋白的有效固定, 并通过蛋白质-整合素相互作用介导细胞的黏附. 微球表面细胞生长增殖后, 其中的二硫键基团可被谷胱甘肽还原, 从而介导细胞无酶无损温和释放. 这种通过调节水凝胶微球表面生物活性分子的固定与释放介导细胞黏附与捕获的新方法为细胞工程提供了一种通用而有效的手段.     

3,5-二硝基苯甲酸酯基改性的HEMA/NVP交联微球对肌酐的吸附特性与吸附机理

制备了平均粒径为180μm的甲基丙烯酸β-羟乙酯(HEMA)与N-乙烯基吡咯烷酮(NVP)交联共聚物微球(HEMA/NVP),使用3,5-二硝基苯甲酰氯(DNBC)对其进行了化学改性,制得了表面键合有大量3,5-二硝基苯甲酸酯基(DNBZ)的功能微球DNBZ-HEMA/NVP;采用红外光谱(FTIR)与化学分析法对其化学结构及组成进行了表征;重点研究了功能微球DNBZ-HEMA/NVP对肌酐的吸附特性与吸附机理.静态吸附实验表明,DNBZ-HEMA/NVP对肌酐具有强的吸附作用,交联微球HEMA/NVP经DNBC化学改性后,对肌酐的吸附容量提高了20倍;DNBZ-HEMA/NVP对肌酐的吸附性能受介质pH值及盐度的影响很大;当pH值较小或较大时,吸附容量都较低,pH=8.5时,吸附容量最大;介质的盐度越大,吸附容量越小.研究结果表明,DNBZ-HEMA/NVP对肌酐的吸附属化学吸附,而且是静电相互作用驱动下的化学吸附.     

Facile synthesis of cucurbit[n]uril derivatives via direct functionalization: expanding utilization of cucurbit[n]uril

A long-standing problem in cucurbituril chemistry is answered through the first direct functionalization of cucurbit[n]uril (CB[n]; n = 5-8)) leading to perhydroxyCB[n] which can be further modified to provide tailored CB[n] derivatives with desired functional groups and good solubility. Anchoring a CB[6] derivative on the surface and its potential application as a sensor are demonstrated. A CB[6] derivative forms nanospheres with possible use in protein and peptide drug delivery.     

The cucurbit[n]uril family: prime components for self-sorting systems

We determined the values of Ka for a wide range of host-guest complexes of cucurbit[n]uril (CB[n]), where n = 6-8, using 1H NMR competition experiments referenced to absolute binding constants measured by UV/vis titration. We find that the larger homologues--CB[7] and CB[8]--individually maintain the size, shape, and functional group selectivity that typifies the recognition behavior of CB[6]. The cavity of CB[7] is found to effectively host trimethylsilyl groups. Remarkably, the values of Ka for the interaction of CB[7] with adamantane derivatives 22-24 exceeds 10(12) M(-1)! The high levels of selectivity observed for each CB[n] individually is also observed for the CB[n] family collectively. That is, the selectivities of CB[6], CB[7], and CB[8] toward a common guest can be remarkably large. For example, guests 1, 3, and 11 prefer CB[8] relative to CB[7] by factors greater than 10(7), 10(6), and 3000, respectively. Conversely, guests 23 and 24 prefer CB[7] relative to CB[8] by factors greater than 5100 and 990, respectively. The high levels of selectivity observed individually and collectively for the CB[n] family renders them prime components for the preparation of functional biomimetic self-sorting systems.     

Surface functionalization and characterization of magnetic polystyrene microbeads

A new approach to the surface functionalization of magnetic polystyrene microbeads with chloroacetyl chloride in the presence of aluminum chloride was reported. Composite microbeads consisting of polymer-coated iron oxide nanoparticles were prepared by spraying suspension polymerization. Functional chloride groups were introduced onto the surface of magnetic polystyrene microbeads by surface chemical reaction without destroying the magnetite nanoparticles within the microbeads. First, a complex was synthesized by a reaction between aluminum chloride and chloroacetyl chloride. Then, the complex was added dropwise to the solution of magnetic polystyrene microbeads, and a surface acylation reaction between complex and polystyrene microbeads was carried out. Subsequently, the amino groups were coupled to the magnetic microbeads via an ammonolysis reaction between ethylenediamine and chloride groups on the acylated magnetic polystyrene microbeads. The chemical composition, surface functional groups, and magnetism of the magnetic polystyrene microbeads before and after surface functionalization were characterized by Fourier transform infrared spectroscopy and vibrating sample magnetometry. The results showed that the surface functionalization reaction had little impact on the magnetism of the microbeads. The content of surface amino groups on the magnetic polystyrene microbeads was found to be 0.2 mmol/g. An affinity dye, Cibacron Blue F3G-A (CB), was then immobilized to prepare a magnetic affinity adsorbent. It was confirmed from X-ray photoelectron spectroscopy spectra that the CB molecules were covalently coupled on the magnetic microbeads.     

Supramolecular nano drug delivery systems mediated via host-guest chemistry of cucurbit[n]uril (n = 6 and 7)

As a novel family of macrocyclic molecules,cucurbit[n]urils(CB[n]s) have emerged as promising building blocks of supramolecular nano drug delivery systems(SNDDS) in recent years.Direct encapsulation of amphiphilic guests by CB[6] and CB[7] can modulate their amphiphilicity,resulting in formation of supramolecular amphiphiles that self-assemble into supramolecular nanoparticles for drug delivery.Additionally,CB[n]'s host-guest chemistry on the surface of mesoporous nanoparticles makes CB[n] an ideal blocking agent to control drug release from delivery vehicles.These SNDDS possess intrinsic stimuli responsiveness towards external guest or host,which can further incorporate re s ponsiveness to a variety of other stimuli including pH,thermal,redox,photo and enzyme,to realize multiple stimuli-responsive drug release.Moreover,the recent breakthrough in direct functionalization of CB[n]s has provided a feasible method for preparing superior CB[6] and CB[7] derivatives that can be employed to build multifunctional SNDDS with unoccupied macrocycles located on surface,which could be decorated with various functional "tags" through host-guest chemistry.In this review,we summarized the recent progress of CB[6] and CB[7] based SNDDS through formation of supramolecular amphiphiles,supramolecular nanovalves as well as supramolecularly tailorable surface,which we hope to further promote the development of CB[n]s family as building blocks for advanced SNDDS.     

功能化PVA-g-PSt微球对牛血清蛋白的吸附研究

由大分子单体法制得了聚醋酸乙烯酯接枝聚苯乙烯(PVAc-g-PSt)微球,使该微球在碱性条件下醇解形成了聚乙烯醇接枝聚苯乙烯(PVA-g-PSt)微球.经X射线光电子能谱对PVA-g-PSt微球表层组成的表征,发现微球具有以PVA为壳、PSt为核的核壳结构.进而利用汽巴蓝F3GA(CB)与PVA-g-PSt微球进行亲核反应,制得了CB功能化的PVA-g-PSt微球,由元素分析定量出了固定在微球表面的CB含量.用透射电子显微镜对微球的粒径与形态进行了表征,发现微球表面在CB功能化后变得相对粗糙,粒径大小基本保持不变,但形态更加规整.比较了3种不同微球对蛋白质的吸附,考察了吸附动力学和影响吸附的因素,发现起始牛血清蛋白(BSA)浓度、pH值、离子强度对微球吸附BSA有明显的影响,并利用Zeta电位探讨了微球与蛋白质间的相互作用机理.最后用硫氰酸钠(NaSCN)进行解吸,计算解吸率最高可达到95.7%,该CB功能化微球可以重复利用,吸附率仅减少5.3%.     

Metal cation-methyl interactions in CB11Me12(-) salts of Me3Ge+, Me3Sn+, and Me3Pb+

Oxidation of Me(6)M(2) (M = Ge, Sn) and Me(4)Pb with the CB(11)Me(12)(*) radical in alkane solvents produced the insoluble salts Me(3)M(+)CB(11)Me(12)(-), characterized by CP-MAS NMR and EXAFS. The cations interact with methyl groups of CB(11)Me(12)(-) with coordination strength increasing from Pb to Ge. Density functional theory (DFT) calculations for the isolated ion pairs, Me(3)M(+)CB(11)Me(12)(-) (M = Ge, Sn), revealed three isomers with the cation above methyl 2, 7, or 12, and not above a BB edge or a BBB triangle. The interaction has a considerable covalent component, with the cation attempting to perform a backside S(E)2 substitution on the methyl carbon. In a fourth less favorable isomer the cation is near methyl 1, inclined toward methyl 2, and interacts with hydrogens. DFT atomic charge distributions and plots of the electrostatic potential on the surface of spheres centered at the CB(11)H(12)(-) and CB(11)Me(12)(-) icosahedra display the effects of uneven charge distribution within the anion and contradict the common belief that the negative charge of the cage anion is concentrated primarily on the cage boron atoms 7-12; in CB(11)Me(12)(-), roughly half is on the cage carbon and the rest on methyls 7-12.     

Study of the surface and interfacial tensions in systems containing a low molar mass liquid crystal

The surface tension of a low molar mass liquid crystal (LMMLC), 4-cyano-4'-n-heptyloxybiphenyl (70CB), was measured as a function of temperature using the pendant drop method, forming drops of different volumes ranging from 5 to 11 mm³. Contact angles formed by drops of 70CB in the nematic and isotropic phases on plates of polystyrene (PS) and of a liquid crystal polymer (LCP), VECTRA A910, were also measured. Only large drops could be used for surface tension analysis. It was shown that in the nematic phase the surface tension of 70CB decreases with increasing temperature, and that in the isotropic phase the surface tension increases with increasing temperature. Using the values of contact angle and of surface tension of 7OCB it was possible to evaluate the interfacial energy between 7OCB and PS and between 7OCB and VECTRA. The interfacial energy between 7OCB and PS, and between 7OCB and VECTRA, decreased with increasing temperature for ranges of temperatures corresponding to both phases of 70CB.     

Study of the surface and interfacial tensions in systems containing a low molar mass liquid crystal

The surface tension of a low molar mass liquid crystal (LMMLC), 4-cyano-4'-n-heptyloxybiphenyl (70CB), was measured as a function of temperature using the pendant drop method, forming drops of different volumes ranging from 5 to 11 mm³. Contact angles formed by drops of 70CB in the nematic and isotropic phases on plates of polystyrene (PS) and of a liquid crystal polymer (LCP), VECTRA A910, were also measured. Only large drops could be used for surface tension analysis. It was shown that in the nematic phase the surface tension of 70CB decreases with increasing temperature, and that in the isotropic phase the surface tension increases with increasing temperature. Using the values of contact angle and of surface tension of 7OCB it was possible to evaluate the interfacial energy between 7OCB and PS and between 7OCB and VECTRA. The interfacial energy between 7OCB and PS, and between 7OCB and VECTRA, decreased with increasing temperature for ranges of temperatures corresponding to both phases of 70CB.     

Surface-functionalized Carbon Black as Catalyst for the Direct Production of Hydrogen Peroxide by the Oxidation of Hydroxylamine

Carbon black (CB) without micropores was functionalized by mixed acid and used to explore the surface chemistry effect on the production of hydrogen peroxide (H₂O₂). The CB materials were characterized by N₂ adsorption‐desorption, XRD, SEM, FTIR, and TPD. The results of different characterization methods indicated that both the textural features and the surface chemical properties of CB were significantly modified by the acidic treatment. The catalytic performance of the modified CBs for hydroxylamine (NH₂OH) oxidation increased with increasing the surface oxygen‐containing species. The yield of H₂O₂ approached 30% with the corresponding concentration of 73.9 mmol·L^?1 (w=0.25%) over the most promising CB catalyst, which was much superior to the results obtained on supported noble metals. Correlations between catalytic activity and concentration of different surface functional groups on the CB samples confirmed that the quinonoid species might be the active species.     

聚合物链长及表面吸附强度对三维受限下嵌段共聚物微观相分离的影响

利用动态密度泛函(Dynamic density functional theory, DDFT)方法研究了三维受限下嵌段共聚物的微观相分离, 讨论了共聚物链长和表面吸附强度对微观相形成与取向的影响. 体系中随机分布的等径微球提供三维限制结构, 体积分数为0.6. 增加微球的半径和体积分数, 能够使其从破坏微相规整结构的纳米掺杂过渡到提供三维限制结构. 调整嵌段共聚物与微球表面的相互作用对微相形成与取向有重要影响.     

Copper-free Sonogashira reaction using 7-chloro camptothecins

We studied copper-free Sonogashira reaction using 7-chloro camptothecins, and determined that rac-BINAP/Pd(OAc)₂ was an efficient catalyst for the coupling reaction. With this process, a number of 7-substituted camptothecins with a wide range of functional groups are potentially accessible. Besides, two drugs, SN-38 and BNP-1350, could be prepared by this method.     

Recognition properties of cucurbit[7]uril self-assembled monolayers studied with force spectroscopy

Specific (host-guest) and unspecific (substrate-guest) interactions between self-assembled monolayers of cucurbit[7]uril (CB[7]) on gold (Au) substrates and neutral adamantyl (Ad) guests were resolved by studying these interactions at the single molecule level using dynamic force spectroscopy. The dissociation rate constants of the Ad-Au and the Ad-CB[7] interactions were 0.3 s(-1) and 0.03 s(-1), respectively, indicating that the specific binding is more stable. The probability of observing a specific interaction (40 ± 9%) is similar to the reported surface coverages of CB[7] monolayers on Au substrates. The higher strength and stability of the Ad-CB[7] interactions explains why, although presenting an imperfect coverage, CB[n] monolayers can be used successfully as a platform for surface immobilization.