Adhesion force studies of Janus nanoparticles

Janus nanoparticles represent a unique nanoscale analogue to the conventional surfactant molecules, exhibiting hydrophobic characters on one side and hydrophilic characters on the other. Yet, direct visualization of the asymmetric surface structures of the particles remains a challenge. In this paper, we used a simple technique based on AFM adhesion force measurements to examine the two distinctly different hemispheres of the Janus particles at the molecular level. Experimentally, the Janus nanoparticles were prepared by ligand exchange reactions at the air-water interface. The particles were then immobilized onto a substrate surface with the particle orientation controlled by the chemical functionalization of the substrate surface, and an AFM adhesion force was employed to measure the interactions between the tip of a bare silicon probe and the Janus nanoparticles. It was found that when the hydrophilic side of the particles was exposed, the adhesion force was substantially greater than that with the hydrophobic side exposed, as the silicon probes typically exhibit hydrophilic properties. These studies provide further confirmation of the amphiphilic nature of the Janus nanoparticles.     

Kinetics study of the binding of multivalent ligands on size-selected gold nanoparticles

The effect of ligand multivalency and nanoparticle size on the binding kinetics of thiol ligands on gold nanoparticles is investigated by exchanging monovalently bound pyrene on gold nanoparticles against flexible mono- and multivalent thiol ligands. Variable-sized gold nanoparticles of 2.2 ± 0.4, 3.2 ± 0.7, and 4.4 ± 0.9 nm diameter are used as substrates. The particles are coated by thiol functionalized pyrene ligands and the binding kinetics of the thiol ligands is studied by time-resolved fluorescence spectroscopy. The effect of multivalency on the binding kinetics is evaluated by comparing the rate constants of ligands of different valency. This comparison reveals that the multivalent ligands are exchanging substantially more rapidly than the monovalent ones. A particle size dependence of the rate constants is also observed, which is used to derive structural information on the binding of the mono- and multivalent ligands to the nanoparticle surface.     

Intraparticle charge delocalization of carbene-functionalized ruthenium nanoparticles manipulated by selective ion binding

Olefin metathesis reactions of carbene-stabilized ruthenium nanoparticles were exploited for the incorporation of multiple functional moieties onto the nanoparticle surface. When the nanoparticles were cofunctionalized with 4-vinylbenzo-18-crown-6 and 1-vinylpyrene, the resulting particles exhibited fluorescence characteristics that were consistent with dimeric pyrene with a conjugated chemical bridge, with three peaks observed in the emission spectra at 391, 410, and 485 nm. The behaviors were ascribed to intraparticle charge delocalization between the pyrene moieties afforded by the conjugated Ru═carbene interfacial linkages. Notably, upon the binding of metal ions in the crown ether cavity, the emission intensity of the nanoparticle fluorescence was found to diminish at 485 nm and concurrently increase at 391 and 410 nm rather markedly, with the most significant effects observed with K(+). This was accounted for by the selective binding of 18-crown-6 to potassium ions, where the positively charged ions led to the polarization of the nanoparticle core electrons that was facililated by the conjugated linkage to the metal surface and hence impeded intraparticle charge delocalization. Control experiments with a pyrene-crown ether conjugate (2) and with ruthenium nanoparticles cofunctionalized with 4-vinylbenzo-18-crown-6 and 1-allylpyrene suggested that the through-bond pathway played a predominant role in the manipulation of intraparticle electronic communication whereas the contributions from simple electrostatic interactions (i.e., through-space pathway) were minimal.     

配体链包覆纳米粒子的表面相分离及自组装的模拟研究

通过耗散粒子动力学方法,模拟了二元配体链包覆的纳米粒子表面的相分离行为,并与现有的模拟和实验体系进行对比.研究结果印证了相分离驱动力是配体链错位所导致的构象熵的结论.进一步以相分离得到的Janus和三嵌段Janus结构纳米粒子作为构筑单元,研究了其在选择性溶剂中的自组装行为.结果表明,Janus粒子易自组装成为双层囊泡结构,而三嵌段Janus粒子则更易形成单层囊泡结构.对于从配体链包覆的纳米粒子出发,设计具有特殊功能的囊泡提供了理论支持.     

Membrane emulsification and solvent pervaporation processes for the continuous synthesis of functional magnetic and Janus nanobeads

We discuss the integration of membrane emulsification and pervaporation processes for the continuous production of functional materials, such as silica-encapsulated magnetite nanoparticle clusters and asymmetric Janus nanoparticles, by the emulsion droplet solvent evaporation method, which has traditionally been performed in small-scale batch systems. An organic solvent containing primary magnetite nanoparticles (～10 nm) coated with oleic acid was dispersed in a continuous aqueous phase by membrane emulsification, which enabled the consistent production of nanoparticle-laden solvent droplets of well-controlled size with narrow size distributions. The solvent was removed from the emulsion by pervaporation. Prior to complete solvent removal, the nanoparticle packing density within the clusters was a function of the residence time in the pervaporation unit. The final clusters formed, ～100-300 nm in size, exhibited the same superparamagnetic behavior as the primary nanoparticles, and were stable in aqueous media with a zeta potential of -70 mV at neutral pH. A facile method was used to coat the nanoclusters with a silica shell, providing sites for surface functionalization with a range of organic ligands. The nanoparticles and clusters were analyzed by a variety of techniques, including TGA, DLS, TEM, EDS, and SQUID. The effects of various parameters, such as the membrane dimensions and flow rate through the unit, on the mass transport rates were elucidated through a parametric modeling study. The applicability of the methods to the production of polymeric beads and more complex particles was demonstrated; to create Janus structures, organic polymer solutions were dispersed as droplets in continuous aqueous phases, and the solvent was subsequently evaporated. The Janus particles consisted either of polymeric cores with magnetite nanoparticles clustered as islands on their surfaces, or of two phase-separated polymers, each constituting half of any given polymeric particle.     

两亲性Janus粒子在蜂窝状多孔聚合物膜上的自组装性能

采用具有两亲性的两面体(Janus)粒子实现稳定的粒子界面组装与水滴模板法自组装过程相结合的方法获得了粒子在蜂窝状多孔聚合物薄膜内壁的高效定向修饰.通过与均质粒子组装形貌的对比,证明了Janus粒子因其特殊的界面自组装活性,可以获得高粒子加量条件下的规则多孔结构,解决了使用均质粒子时存在的结构有序性和粒子修饰密度之间的矛盾.而在较低粒子加量的条件下,Janus粒子也展示出与均质粒子极为不同的组装形貌.这一方法的建立,为新型表面功能化材料的制备提供了一个新的思路.     

Bioconjugation of ultrabright semiconducting polymer dots for specific cellular targeting

Semiconducting polymer dots (Pdots) represent a new class of ultrabright fluorescent probes for biological imaging. They exhibit several important characteristics for experimentally demanding in vitro and in vivo fluorescence studies, such as their high brightness, fast emission rate, excellent photostability, nonblinking, and nontoxic feature. However, controlling the surface chemistry and bioconjugation of Pdots has been a challenging problem that prevented their widespread applications in biological studies. Here, we report a facile yet powerful conjugation method that overcomes this challenge. Our strategy for Pdot functionalization is based on entrapping heterogeneous polymer chains into a single dot, driven by hydrophobic interactions during nanoparticle formation. A small amount of amphiphilic polymer bearing functional groups is co-condensed with the majority of semiconducting polymers to modify and functionalize the nanoparticle surface for subsequent covalent conjugation to biomolecules, such as streptavidin and immunoglobulin G (IgG). The Pdot bioconjugates can effectively and specifically label cellular targets, such as cell surface marker in human breast cancer cells, without any detectable nonspecific binding. Single-particle imaging, cellular imaging, and flow cytometry experiments indicate a much higher fluorescence brightness of Pdots compared to those of Alexa dye and quantum dot probes. The successful bioconjugation of these ultrabright nanoparticles presents a novel opportunity to apply versatile semiconducting polymers to various fluorescence measurements in modern biology and biomedicine.     

A core-shell nanoparticle approach to photoreversible fluorescence modulation of a hydrophobic dye in aqueous media

Amphiphilic core-shell nanoparticles containing spiropyran moieties have been prepared in aqueous media. The nanoparticles consist of hydrophilic and biocompatible poly(ethyleneimine) (PEI) chain segments, which serve as the shell, and a hydrophobic copolymer of methyl methacrylate (MMA), a spiropyran-linked methacrylate, and a cross-linker, which forms the core of the nanoparticles. A hydrophobic fluorescent dye based on the nitrobenzoxadiazolyl (NBD) group was introduced into the nanoparticles to form NBD-nanoparticle complexes in water. The nanoparticles not only greatly enhance the fluorescence emission of the hydrophobic dye NBD in aqueous media, probably by accommodating the dye molecules in the interface between the hydrophilic shells and the hydrophobic cores, but also modulate the fluorescence of the dye through intraparticle energy transfer. This biocompatible and photoresponsive nanoparticle complex may find applications in biological areas such as biological diagnosis, imaging, and detection. In addition, this nanoparticle approach will open up possibilities for the fluorescence modulation of other hydrophobic fluorophores in aqueous media.     

Reversible "irreversible" inhibition of chymotrypsin using nanoparticle receptors

Anionically functionalized amphiphilic nanoparticles efficiently inhibit chymotrypsin through electrostatic binding followed by protein denaturation. We demonstrate the ability to disrupt this "irreversible" inhibition of chymotrypsin through modification of the nanoparticle surface using cationic surfactants. Up to 50% of original chymotrypsin activity is rescued upon long-chain surfactant addition. Dynamic light-scattering studies demonstrate that chymotrypsin is released from the nanoparticle surface. The conformation of the rescued chymotrypsin was characterized by fluorescence and fluorescence anisotropy, indicating that chymotrypsin regains a high degree of native structure upon surfactant addition.     

Hybrid fluorescent nanoparticles fabricated from pyridine-functionalized polyfluorene-based conjugated polymer as reversible pH probes over a broad range of acidity-alkalinity

Conjugated polymer nanoparticles (CPNs) were developed based on a polyfluorene-based conjugated polymer with thiophene units carrying pyridyl moieties incorporated in the backbone of polymer chains (PFPyT). Hybrid CPNs fabricated from PFPyT and an amphiphilic polymer (NP1) displayed pH-sensitive fluorescence emission features in the range from pH 4.8 to 13, which makes them an attractive nanomaterial for wide range optical sensing of pH values. The fluorescence of hybrid CPNs based on chemically close polyfluorene derivatives without pyridyl moieties (NP3), in contrast, remains virtually unperturbed by pH values in the same range. The fluorescence emission features of NP1 underwent fully reversible changes upon alternating acidification/basification of aqueous dispersions of the CPNs and also displayed excellent repeatability. The observed pH sensing properties of NP1 are attributed to protonation/deprotonation of the nitrogen atoms of the pyridine moieties. This, in turn, leads to the redistribution of electron density of pyridine moieties and their participation in the π-conjugation within the polymer main chains. The optically transparent amphiphilic polymers also exerted significant influence on the pH sensing features of the CPNs, likely by acting as proton sponge and/or acid chaperone. Figure

pH-sensitive fluorescent nanoparticles were fabricated from pyridine-functionalized conjugated polymer; protonation/deprotonation of the nitrogen atoms of pyridine moieties upon pH changes, which leads to the redistribution of electron density of pyridine moieties and their participation in the π-conjugation with polymer chains, were confirmed.     

Preparation and controlled self-assembly of Janus magnetic nanoparticles

Janus magnetic nanoparticles (~20 nm) were prepared by grafting either polystyrene sodium sulfonate (PSSNa) or polydimethylamino ethylmethacrylate (PDMAEMA) to the exposed surfaces of negatively charged poly(acrylic acid) (PAA)-coated magnetite nanoparticles adsorbed onto positively charged silica beads. Individually dispersed Janus nanoparticles were obtained by repulsion from the beads on reversal of the silica surface charge when the solution pH was increased. Controlled aggregation of the Janus nanoparticles was observed at low pH values, with the formation of stable clusters of approximately 2-4 times the initial size of the particles. Cluster formation was reversed, and individually dispersed nanoparticles recovered, by restoring the pH to high values. At intermediate pH values, PSSNa Janus nanoparticles showed moderate clustering, while PDMAEMA Janus nanoparticles aggregated uncontrollably due to dipolar interactions. The size of the stable clusters could be controlled by increasing the molecular weight of the grafted polymer, or by decreasing the magnetic nanoparticle surface availability for grafting, both of which yielded larger cluster sizes. The addition of small amounts of PAA-coated magnetic nanoparticles to the Janus nanoparticle suspension resulted in a further increase in the final cluster size. Monte Carlo simulation results compared favorably with experimental observations and showed the formation of small, elongated clusters similar in structure to those observed in cryo-TEM images.     

Janus Nanoparticles: Preparation,Characterization, and Applications

In chemical functionalization of colloidal particles, the functional moieties are generally distributed rather homogeneously on the particle surface. Recently, a variety of synthetic protocols have been developed in which particle functionalization may be carried out in a spatially controlled fashion, leading to the production of structurally asymmetrical particles. Janus particles represent the first example in which the two hemispheres exhibit distinctly different chemical and physical properties, which is analogous to the dual‐faced Roman god, Janus. Whereas a variety of methods have been reported for the preparation of (sub)micron‐sized polymeric Janus particles, it has remained challenging for the synthesis and (unambiguous) structural characterization of much smaller nanometer‐sized Janus particles. Herein, several leading methods for the preparation of nanometer‐sized Janus particles are discussed and the important properties and applications of these Janus nanoparticles in electrochemistry, sensing, and catalysis are highlighted. Some perspectives on research into functional patchy nanoparticles are also given.     

载药荧光纳米粒子的制备及在乳腺癌MCF-7细胞系的应用及效果评价

利用两亲性聚乙二醇-聚乳酸共聚物（PEG-PDLLA）包覆荧光染料（DPBA）和紫杉醇（PTX）,通过自组装方法制得载药荧光纳米粒子DPBA/PTX@PEG-PDLLA.纳米粒子尺寸均一,具有良好的生物相容性.对纳米粒子的发光性质、载药量和体外药物释放等进行了表征,并考察了纳米粒子对乳腺癌细胞MCF-7的抑制效果,观察了MCF-7细胞对纳米粒子的摄取情况.结果表明,DPBA/PTX@PEG-PDLLA纳米粒子具有较强的红光发射,不仅可以用于MCF-7肿瘤细胞质荧光成像,而且对肿瘤细胞的增殖具有一定的抑制能力.     

Pre- and postfunctionalized self-assembled π-conjugated fluorescent organic nanoparticles for dual targeting

There is currently a high demand for novel approaches to engineer fluorescent nanoparticles with precise surface properties suitable for various applications, including imaging and sensing. To this end, we report a facile and highly reproducible one-step method for generating functionalized fluorescent organic nanoparticles via self-assembly of prefunctionalized π-conjugated oligomers. The engineered design of the nonionic amphiphilic oligomers enables the introduction of different ligands at the extremities of inert ethylene glycol side chains without interfering with the self-assembly process. The intrinsic fluorescence of the nanoparticles permits the measurement of their surface properties and binding to dye-labeled target molecules via F?rster resonance energy transfer (FRET). Co-assembly of differently functionalized oligomers is also demonstrated, which enables the tuning of ligand composition and density. Furthermore, nanoparticle prefunctionalization has been combined with subsequent postmodification of azide-bearing oligomers via click chemistry. This allows for expanding ligand diversity at two independent stages in the nanoparticle fabrication process. The practicability of the different methods entails greater control over surface functionality. Through labeling with different ligands, selective binding of proteins, bacteria, and functionalized beads to the nanoparticles has been achieved. This, in combination with the absence of unspecific adsorption, clearly demonstrates the broad potential of these nanoparticles for selective targeting and sequestration. Therefore, controlled bifunctionalization of fluorescent π-conjugated oligomer nanoparticles represents a novel approach with high applicability to multitargeted imaging and sensing in biology and medicine.     

Fluorescent Metallacycle-Cored Amphiphilic Nanoparticles Formed by β-Cyclodextrin-Based Host–Guest Interactions towards Cancer Theranostics

Theranostic agents, taking the advantages of both imaging and therapeutic functions, are anticipated to be key components in the development of personalized medicine in which the therapeutic response can be real-time monitored. Herein, three metallacycles with pendent adamantane groups are prepared by coordination-driven self-assembly of Pt^II ligands with anticancer activities and tetraphenylethylene derivatives with emission. β-Cyclodextrin, which shows good host–guest interactions with adamantane moieties, was added to form amphiphilic supramolecular nanoparticles with the aim to enhance the aqueous solubilities and bioactivities of these metallacycles. Moreover, when rhodamine-modified β-cyclodextrin was used as the carrier, the release of the metallacycles from the nanoparticles could be monitored in situ through the fluorescence changes owing to the efficient fluorescence resonance energy transfer from the metallacycles to rhodamine-modified β-cyclodextrin. In vitro and in vivo studies showed that these nanoparticles not only served as cell imaging contrast agents but also displayed improved anticancer activities, allowing them to serve as potential candidates for cancer theranostics. This study provides a simple and efficient method to prepare theranostic agents by hierarchical supramolecular self-assembly, which will pave the way for image-guided cancer therapy, targeted cancer therapy, and related biomedical fields.     

Preparation, characterization and application of pyrene-loaded methoxy poly(ethylene glycol)–poly(lactic acid) copolymer nanoparticles

Pyrene-loaded biodegradable polymer nanoparticles were prepared by incorporating pyrene into the polymer nanoparticles formulated from amphiphilic diblock copolymer, methoxy poly(ethylene glycol)–poly(lactic acid) (MePEG–PLA). Their morphological structure and physical properties were characterized by nuclear magnetic resonance (NMR), dynamic light scattering, fluorescence spectroscopy, transmission electronic microscopy and zeta potential measurements. Further, MePEG–PLA nanoparticles containing pyrene as fluorescent marker were administered intranasally to rats, and the distribution of nanoparticles in the nasal mucosa and the olfactory bulb were visualized by fluorescence microscopy. NMR results confirmed that MePEG–PLA copolymer can form nanoparticles in water, and hydrophilic PEG chains were located on the surface of the nanoparticles. The particle size, zeta potential and pyrene loading efficiency of MePEG–PLA nanoparticles were dependent on the PLA block content in the copolymer. Following nasal administration, the absorption of nanoparticles across the epithelium was rapid, with fluorescence observed in the olfactory bulb at 5 min, and a higher level of fluorescence persisted in the olfactory mucosa than that in the respiratory mucosa. These results show that pyrene could serve as a useful fluorescence probe for incorporation into polymer nanoparticles to study tissue distribution and MePEG–PLA nanoparticles might have a great potential as carriers of hydrophobic drugs.     

Adsorption characteristics of thionine on gold nanoparticles

Adsorption characteristics of thionine on gold nanoparticles have been studied by using UV-vis absorption spectroscopy, fluorescence spectroscopy, transmission electron microscopy (TEM), cyclic voltammetry and Fourier transform infrared spectroscopy. With the increasing concentration of gold nanoparticles, the absorption peak intensity of H-type dimers of thionine increases continuously, whereas that of monomers of thionine first increases and then decreases. The addition of gold nanoparticles makes the equilibrium between the monomer and H-type dimer forms of thionine move toward the dimer forms. Furthermore, the adsorption behavior of thionine on gold nanoparticles is also influenced by temperature. TEM images show that the addition of thionine results in an obvious aggregation, and further support the absorption spectral results. The fluorescence intensity of adsorbed thionine is quenched by gold nanoparticles due to the electronic interaction between thionine molecules and gold nanoparticles. Cyclic voltammetric and infrared spectroscopic studies show that the nitrogen atoms of both of the NH2 moieties of thionine strongly bind to the gold nanoparticle surfaces through the electrostatic interaction of thionine with gold nanoparticles. For 15-20 nm particles, the number of adsorbed thionine molecules per gold nanoparticle is about 7.66 x 10(4). Thionine molecules can not only bind to a particle to form a compact monolayer via both of the NH2 moieties, but they can also bind to two particles via their two NH(2) moieties, respectively.     

两亲性Janus粒子的合成及其在Pickering乳液中的应用

Janus粒子由于在光、电、力、磁及表面亲/疏水性等方面表现出各向异性,因此在稳定乳液、生物医药及功能涂层等方面展现出广阔的应用价值。两亲性Janus粒子是指一侧具有亲水性、另一侧具有疏水性的不对称材料,由于同时具有表面活性剂的性质和固体颗粒的效应,在稳定Pickering乳液方面极具优势。基于此,本文对两亲性Janus粒子的制备方法进行了综述,并对比分析了其优缺点,同时总结了两亲性Janus粒子对Pickering乳液稳定性的影响,最后对其今后的发展进行了展望。     

Extinction coefficient of gold nanoparticles with different sizes and different capping ligands

Extinction coefficients of gold nanoparticles with core size ranging from approximately 4 to 40 nm were determined by high resolution transmission electron microscopy analysis and UV-vis absorption spectroscopic measurement. Three different types of gold nanoparticles were prepared and studied: citrate-stabilized nanoparticles in five different sizes; oleylamide-protected gold nanoparticles with a core diameter of 8 nm, and a decanethiol-protected nanoparticle with a diameter of around 4 nm. A linear relationship between the logarithms of extinction coefficients and core diameters of gold particles was found independent of the capping ligands on the particle surface and the solvents used to dissolve the nanoparticles. This linear relation may be used as a calibration curve to determine the concentration or average size of an unknown nanoparticle or nanoparticle-biomolecule conjugate sample.     

Stimuli induced structural changes of gold nanoparticle assemblies having sequential alternating amphiphilic peptides at the surface

Gold nanoparticles having sequential alternating amphiphilic peptide chains, Phe-(Leu-Glu)8, on the surface have been prepared. We describe structural control of the amphiphilic peptide coated gold nanoparticle assembly by a conformational transition of the surface peptides. Under the acidic condition, the conformation of the surface amphiphilic peptide was converted to a beta-sheet structure from an aggregated alpha-helix by incubation. Under this condition, the amphiphilic peptide coated gold nanoparticles formed a nanosheet assembly. The plasmon absorption maximum of the gold nanoparticles shifted to a shorter wavelength with the formation of the beta-sheet assembly of the surface peptide. This suggests that the structure of the peptide coated gold nanoparticle assembly could be controlled by the conformational transition of the surface peptide. Furthermore, the core gold nanoparticle could be fixed in the beta-sheet assembly in the state that stood alone. This system may be useful for novel molecular devices that exhibit quantized properties.