Polymeric Nanoparticles Amenable to Simultaneous Installation of Exterior Targeting and Interior Therapeutic Proteins

Effective delivery of therapeutic proteins is a formidable challenge. Herein, using a unique polymer family with a wide‐ranging set of cationic and hydrophobic features, we developed a novel nanoparticle (NP) platform capable of installing protein ligands on the particle surface and simultaneously carrying therapeutic proteins inside by a self‐assembly procedure. The loaded therapeutic proteins (e.g., insulin) within the NPs exhibited sustained and tunable release, while the surface‐coated protein ligands (e.g., transferrin) were demonstrated to alter the NP cellular behaviors. In vivo results revealed that the transferrin‐coated NPs can effectively be transported across the intestinal epithelium for oral insulin delivery, leading to a notable hypoglycemic response.     

Design and Applications of Protein‐Cage‐Based Nanomaterials

Materials science is beginning to focus on biotemplation, and in support of that trend, it is realized that protein cages—proteins that assemble from multiple monomers into architectures with hollow interiors—can instill a number of unique advantages to nanomaterials. In addition, the structural and functional plasticity of many protein‐cage systems permits their engineering for specific applications. In this review, the most commonly used viral and non‐viral protein cages, which exhibit a wide diversity of size, functionality, and chemical and thermal stabilities, are described. Moreover, how they have been exploited for nanomaterial and nanotechnology applications is summarized.     

纳米粒子的控制生长和自组装研究进展

由于在纳米器件上潜在应用,通过化学方法控制的纳米粒子生长,以及纳米粒子自组装的一维、二维和三维点阵受到人们的广泛关注。本文介绍来近年来纳米粒子的控制生长和组装研究的现状。主要探讨了有机稳定剂对纳米粒子形状和尺寸控制的影响。含配位基团和长链烷烃的有机化合物不但可以用控制纳米粒子生长的稳定剂,而且可以用作纳米粒子自组装的模板剂。     

Nucleation of Tiny Silver Nanoparticles by Using a Tetrafacial Organic Molecular Barrel: Potential Use in Visible-Light-Triggered Photocatalysis

Coordination-driven self-assembly of discrete molecular architectures of diverse shapes and sizes has been well studied in the last three decades. Use of dynamic imine bonds for designing analogous metal-free architectures has become a growing challenge recently. This article reports an organic molecular barrel ( OB4^R ) as a potential template for nucleation and stabilization of very tiny (<1.5 nm) Ag nanoparticles (AgNPs). Imine bond condensation of a rigid tetra-aldehyde with a flexible diamine followed by imine-bond reduction yielded the discrete tetragonal organic barrel ( OB4^R ). The presence of a molecular pocket ornamented with eight diamine moieties gives the potential for encapsulation of silver(I). The organic barrel was finally used as a molecular vessel for the controlled nucleation of silver nanoparticles (AgNPs) with fine size tuning through binding of Ag^I ions in the confined space of the barrel followed by reduction. Transmission electron microscopy (TEM) analysis of the Ag⁰@OB4^R composite revealed that the mean particle size is 1.44±0.16 nm. The composite material has approximately 52 wt % silver loading. The barrel-supported ultrafine AgNPs [ Ag⁰@OB4^R ] are found to be an efficient photocatalyst for facile Ullmann-type aryl-amination coupling of haloarenes at ambient temperature without using any additives. The catalyst was stable for several cycles of reuse without any agglomeration. The new composite Ag⁰@OB4^R represents the first example of discrete organic barrel-supported AgNPs employed as a photocatalyst in Ullmann-type coupling reactions at room temperature.     

Protein–Nanoparticle Interaction‐Induced Changes in Protein Structure and Aggregation

Large surface area, small size, strong optical properties, controllable structural features, variety of bioconjugation chemistries, and biocompatibility make many different types of nanoparticles (NPs), such as gold NPs, useful for many biological applications, such as biosensing, cellular imaging, disease diagnostics, drug delivery, and therapeutics. Recently, interactions between proteins and NPs have been extensively studied to understand, control, and utilize the interactions involved in biomedical applications of NPs and several biological processes, such as protein aggregation, for many diseases, including Alzheimer's disease. These studies also offer fundamental knowledge on changes in protein structure, protein aggregation mechanisms, and ways to unravel the roles and fates of NPs within the human body. This review focuses on recent studies on the roles and uses of NPs in protein structural changes and aggregation processes.     

纳米荧光小球标记在蛋白质微阵列检测中的应用研究

研究了不经分离、一次性制备氨基化联吡啶钌掺杂的双层二氧化硅纳米小球的方法。实验证明该纳米小球尺寸均匀,光稳定性、水溶性好,分散稳定。通过简单的偶联反应后,它能有效的和蛋白质结合,结合后的蛋白能保持其生物活性。以此纳米荧光小球为标记物,应用于蛋白质微阵列的定量检测,结果发现其效果明显优于相同条件下以异硫氰酸荧光素(FITC)为标记物的定量结果,检出限可以达到3.5 mg/L。     

Self‐Assembly Behaviors of a Penta‐Phenylene Maltoside and Its Application for Membrane Protein Study

We prepared an amphiphile with a penta‐phenylene lipophilic group and a branched trimaltoside head group. This new agent, designated penta‐phenylene maltoside (PPM), showed a marked tendency to self‐assembly into micelles via strong aromatic–aromatic interactions in aqueous media, as evidenced by ¹H NMR spectroscopy and fluorescence studies. When utilized for membrane protein studies, this new agent was superior to DDM, a gold standard conventional detergent, in stabilizing multiple proteins long term. The ability of this agent to form aromatic–aromatic interactions is likely responsible for enhanced protein stabilization when associated with a target membrane protein.     

Preparation and Self-assembly of Zirconia Nanoparticles via Hydrothermal Method

Zirconia nanoparticles were synthesized via hydrothermal method without any additives. This work focuses on the effect of preparation conditions1 such as the precursor preparation condition and crystallization time of nanocrystallite in autoclave on the properties of as-prepared products. The results indicated that the amount of tetragonal zirconia varied with the preparation conditions. It increased with the increase of the concentration of KOH solution in precursor producing process and reduced with the prolongation of crystallization time. At the same time, the particle size and morphology were also affected by the preparation conditions. In addition, the self-assembled spindle- like aggregates were observed in present works.     

空壳纳米金修饰的新型DNA传感器

利用新型材料金纳米空球, 通过层层修饰的技术, 分别将壳聚糖、空壳纳米金、L-半胱氨酸、细胞色素c以及ssDNA探针修饰到玻碳电极表面, 制备了一种新型的DNA生物传感器. 以紫外及透射电子显微镜(TEM)表征了空壳纳米金, 以循环伏安法、阻抗谱图等电化学方法研究了传感器的特性, 通过原子力显微镜方法观察了该DNA生物传感器不同层之间的形态差异. 结果表明, 该修饰电极所吸附的ssDNA探针为1.672×10^―10 mol•cm^－2. 在指示剂柔红霉素的帮助下, DNA探针可与互补的DNA进行杂交, 借此以微分脉冲伏安法测定DNA.     

The Influence of Surface Composition of Nanoparticles on their Interactions with Serum Albumin

Interactions between differently functionalised silver and gold nanoparticles (NPs) as well as polystyrene nanoparticles with bovine serum albumin (BSA) are studied using circular dichroism (CD) spectroscopy. It is found that the addition of NPs to the protein solution destroys part of the helical secondary structure of the protein as a result of surface adsorption. From the loss of free protein and hence the extent of their structural change adsorption equilibrium constants are derived. The results reveal that citrate‐coated gold and silver NPs exhibit much stronger interactions with BSA than polymeric or polymer‐coated metallic NPs. It is therefore concluded that for the particles considered, the influence of surface composition on the interaction behaviour dominates that of the core.     

Foldable Detergents for Membrane Protein Study: Importance of Detergent Core Flexibility in Protein Stabilization

Membrane proteins are of biological and pharmaceutical significance. However, their structural study is extremely challenging mainly due to the fact that only a small number of chemical tools are suitable for stabilizing membrane proteins in solution. Detergents are widely used in membrane protein study, but conventional detergents are generally poor at stabilizing challenging membrane proteins such as G protein-coupled receptors and protein complexes. In the current study, we prepared tandem triazine-based maltosides (TZMs) with two amphiphilic triazine units connected by different diamine linkers, hydrazine (TZM−Hs) and 1,2-ethylenediamine (TZM−Es). These TZMs were consistently superior to a gold standard detergent (DDM) in terms of stabilizing a few membrane proteins. In addition, the TZM−Es containing a long linker showed more general protein stabilization efficacy with multiple membrane proteins than the TZM−Hs containing a short linker. This result indicates that introduction of the flexible1,2-ethylenediamine linker between two rigid triazine rings enables the TZM−Es to fold into favourable conformations in order to promote membrane protein stability. The novel concept of detergent foldability introduced in the current study has potential in rational detergent design and membrane protein applications.     

Fabrication and Characterization of Chitosan–Pea Protein Isolate Nanoparticles

Chitosan (CS) and pea protein isolate (PPI) were used as raw materials to prepare nanoparticles. The structures and functional properties of the nanoparticles with three ratios (1:1, 1:2 1:3, CS:PPI) were evaluated. The particle sizes of chitosan–pea protein isolate (CS–PPI) nanoparticles with the ratios of 1:1, 1:2, and 1:3 were 802.95 ± 71.94, 807.10 ± 86.22, and 767.75 ± 110.10 nm, respectively, and there were no significant differences. Through the analysis of turbidity, endogenous fluorescence spectroscopy and Fourier transform infrared spectroscopy, the interaction between CS and PPI was mainly caused by electrostatic mutual attraction and hydrogen bonding. In terms of interface properties, the contact angles of nanoparticles with the ratio of 1:1, 1:2, and 1:3 were 119.2°, 112.3°, and 107.0°, respectively. The emulsifying activity (EAI) of the nanoparticles was related to the proportion of protein. The nanoparticle with the ratio of 1:1 had the highest potential and the best thermal stability. From the observation of their morphology by transmission electron microscopy, it could be seen that the nanoparticles with a ratio of 1:3 were the closest to spherical. This study provides a theoretical basis for the design of CS–PPI nanoparticles and their applications in promoting emulsion stabilization and the delivery of active substances using emulsions.     

纳米粒子的界面自组装

近年来,随着纳米技术的发展及Pickering乳液在食品、化妆品、医药等领域中的应用,纳米粒子的界面自组装现象引起了人们的广泛关注。界面能的降低是纳米粒子液液界面自组装的主要驱动力。通过改变纳米粒子的尺寸和表面配体的化学性质,可控制纳米粒子的界面自组装行为。本文综述了不同类型纳米粒子实现界面自组装的研究工作,包括均质纳米粒子、Janus纳米粒子、棒状纳米粒子以及生物纳米粒子。最后,对纳米粒子的界面组装这一领域的可能发展做了展望。     

Protein Denaturation Through the Use of Magnetic Molecularly Imprinted Polymer Nanoparticles

The inhibition of the protein function for therapeutic applications remains challenging despite progress these past years. While the targeting application of molecularly imprinted polymer are in their infancy, no use was ever made of their magnetic hyperthermia properties to damage proteins when they are coupled to magnetic nanoparticles. Therefore, we have developed a facile and effective method to synthesize magnetic molecularly imprinted polymer nanoparticles using the green fluorescent protein (GFP) as the template, a bulk imprinting of proteins combined with a grafting approach onto maghemite nanoparticles. The hybrid material exhibits very high adsorption capacities and very strong affinity constants towards GFP. We show that the heat generated locally upon alternative magnetic field is responsible of the decrease of fluorescence intensity.     

“Precipitation on Nanoparticles”: Attractive Intermolecular Interactions Stabilize Specific Ligand Ratios on the Surfaces of Nanoparticles

Confining organic molecules to the surfaces of inorganic nanoparticles can induce intermolecular interactions between them, which can affect the composition of the mixed self‐assembled monolayers obtained by co‐adsorption from solution of two different molecules. Two thiolated ligands (a dialkylviologen and a zwitterionic sulfobetaine) that can interact with each other electrostatically were coadsorbed onto gold nanoparticles. The nanoparticles favor a narrow range of ratios of these two molecules that is largely independent of the molar ratio in solution. Changing the solution molar ratio of the two ligands by a factor of 5 000 affects the on‐nanoparticle ratio of these ligands by only threefold. This behavior is reminiscent of the formation of insoluble inorganic salts (such as AgCl), which similarly compensate positive and negative charges upon crystallizing. Our results pave the way towards developing well‐defined hybrid organic–inorganic nanostructures.     

Reversible Self-Assembly of Gold Nanoparticles Based on Co-Functionalization with Zwitterionic and Cationic Binding Motifs**

We report a pH- and temperature-controlled reversible self-assembly of Au-nanoparticles (AuNPs) in water, based on their surface modification with cationic guanidiniocarbonyl pyrrole (GCP) and zwitterionic guanidiniocarbonyl pyrrole carboxylate (GCPZ) binding motifs. When both binding motifs are installed in a carefully balanced ratio, the resulting functionalized AuNPs self-assemble at pH 1, pH 7 and pH 13, whereas they disassemble at pH 3 and pH 11. Further disassembly can be achieved at elevated temperatures at pH 1 and pH 13. Thus, we were able to prepare functionalized nanoparticles that can be assembled/disassembled in seven alternating regimes, simply controlled by pH and temperature.     

银/铂双金属中空纳米颗粒的制备及光学性质研究

通过以Ag纳米颗粒为模板的置换和沉积反应,制备了Ag/Pt双金属复合纳米颗粒.用透射电子显微镜(TEM)对颗粒的形貌、尺寸和结构进行了表征,发现复合颗粒具有中空结构.紫外可见吸收光谱(UV-Vis)研究表明,Ag/Pt双金属中空复合纳米颗粒具有单峰的表面等离子共振吸收特征,随着反应溶液中氯铂酸和硝酸银摩尔比的增加,吸收峰先红移后蓝移.表面增强拉曼光谱实验结果表明,Ag/Pt双金属复合纳米颗粒对吡啶分子具有较好的增强效果.     

纳米粒子微囊的界面自组装

微囊是一类重要的功能性材料,在生物医药研究领域有重要用途。微囊的囊壁构建材料一般为脂质体和聚合物。以纳米粒子作为囊壁可将纳米粒子独特的物理化学性质整合到微囊中,使微囊具有机械强度高、渗透性可控、表面易于修饰和容易实现负载物的可控释放等特点,这种新型微囊在生物转运研究领域有潜在的应用前景。本文综述了以纳米粒子作为囊壁的微囊自组装研究进展,介绍了微囊自组装基本理论、囊壁的构建方法、微囊多分散性的改善方法,最后对纳米级微囊的自组装所面临的技术难点进行了讨论,并对纳米级微囊自组装的发展方向进行了展望。     

层层自组装纳米金与乙酰胆碱酯酶电化学生物传感器检测有机磷农药

采用层层自组装技术制备了快速检测有机磷农药的生物传感器,利用带正电荷的高分子聚电解质聚二烯丙基二甲基氯化铵(PDDA)将乙酰胆碱酯酶(AChE)和金纳米粒子(AuNPs)通过静电力逐层固定到玻碳电极(GCE)表面,并采用交流阻抗和微分脉冲伏安法研究了此生物传感器的电化学行为。由于金纳米粒子优异的电催化性能和良好的生物相容性,使固定化的乙酰胆碱酯酶对其底物具有更高的亲和力和更快的响应速度。实验结果表明:修饰金纳米粒子后,传感器的氧化电流明显增大,在4.6×10-5～5.3×10-3mol/L范围内,固定化酶的抑制率与甲基对硫磷浓度的对数成正比,检出限为7.6×10-6mol/L。该生物传感器具有制备方法简便、成本低、灵敏度高等优点,已成功用于蔬菜样品中甲基对硫磷含量的测定。