Facile Functionalization of Gold Nanoparticles with PLGA Polymer Brushes and Efficient Encapsulation into PLGA Nanoparticles: Toward Spatially Precise Bioimaging of Polymeric Nanoparticles

Nanocarriers prepared from poly(lactide‐co‐glycolide) (PLGA) have broad biomedical applications. Understanding their cellular uptake and distribution requires appropriate visualization in complex biological compartments with high spatial resolution, which cannot be offered by traditional imaging techniques based on fluorescent or radioactive probes. Herein, the encapsulation of gold nanoparticles (GNPs) into PLGA nanoparticles is proposed, which should allow precise spatial visualization in cells using electron microscopy. Available protocols for encapsulating GNPs into polymeric matrices are limited and associated with colloidal instability and low encapsulation efficiency. In this report, the following are described: 1) a facile protocol to functionalize GNPs with PLGA polymer followed by 2) encapsulation of the prepared PLGA‐capped GNPs into PLGA nanocarriers with 100% encapsulation efficiency. The remarkable encapsulation of PLGA‐GNPs into PLGA matrix obeys the general rule in chemistry “like dissolves like” as evident from poor encapsulation of GNPs capped with other polymers. Moreover, it is shown that how the encapsulated gold nanoparticles serve as nanoprobes to visualize PLGA polymeric hosts inside cancer cells at the spatial resolution of the electron microscope. The described methods should be applicable to a wide range of inorganic nanoprobes and provide a new method of labeling pharmaceutical polymeric nanocarriers to understand their biological fate at high spatial resolution.     

Bimetallic Nanoparticles with Exotic Facet Structures via Iodide‐Assisted Reduction of Palladium

Iodide is arguably the most challenging halide to control as a shape‐directing additive in metal nanoparticle synthesis and the addition of iodide during bimetallic nanoparticle growth often leads to inhomogeneously stellated products. Through judicious control of low micromolar concentrations of iodide ions in solution in a seed‐mediated approach, alloyed gold–palladium tetradecapod nanoparticles have been synthesized with a mixture of both well‐defined convex and concave surfaces. Notably, these particles are uniform and symmetrical, and this unusual combination of convex and concave features in a single nanostructure is not simply an artifact of intersecting spikes, as would be the case with stellated particles. Further, an important new role for iodide in catalyzing the reduction of palladium ions is identified, particularly at the edge sites of the growing gold nanoparticles. This differs from the commonly accepted theory that iodide slows metal ion reduction, and thus opens up promising new routes to the synthesis of other bimetallic nanoparticles with exotic shapes and surface structures.     

A Comparative Study of Chemical Routes for Coating Gold Nanoparticles via Controlled RAFT Emulsion Polymerization

The synthesis of core‐shell Au nanoparticles protected by an amphiphilic block copolymer is investigated by distinct reversible addition fragmentation chain transfer (RAFT) emulsion polymerization routes. The controlled polymerization of polymer shells onto Au nanoparticles is attempted by using the macroRAFT (MR) agent based on 2‐(dodecylthiocarbonothioylthio)‐2‐methylpropionic acid synthesized via RAFT polymerization of poly(ethylene glycol) methyl ether acrylate and exploring several approaches, which include (i) post‐modification; (ii) in situ synthesis and (iii) “grafting from” strategies. In the conditions investigated here all these strategies lead to Au polymer nanocomposites but morphological well‐defined core‐shell nanoparticles are only obtained by applying the “grafting from” strategy. In particular, conditions that promote chain extension from the MR agent adsorbed onto the Au nanoparticles are found necessary to obtain nanostructures with such morphological characteristics and that still show the localized surface plasmon resonance typical of colloidal Au nanoparticles.     

胶体金纳米颗粒的表面等离子体发射特性

利用电化学方法制备出粒径为20-80 nm的胶体金纳米颗粒。研究其荧光发射光谱特性,在485nm处观察到表面自由电子集体激发导致的表面等离子体共振发射峰,其位置不随激励光波长的变化而移动。当激励光波长为485 nm时,观察到最强的发射峰。在240和640 nm处,还观察到倍频发射峰和3/4分频发射峰。增加金纳米颗粒粒径,观察到发射谱的峰值增大而发射峰的位置只有很小的红移。     

Nanoparticles: Implication of Ligand Choice on Surface Properties,Crystal Structure,and Magnetic Properties of Iron Nanoparticles (Part. Part. Syst. Charact. 3/2013)

The behavior of iron nanoparticles is heavily influenced by their highly reactive surfaces. A better understanding of organic ligand/particle interactions must be achieved in order to synthesize iron nanoparticles with magnetic saturations (σ _sat) equivalent to bulk iron. Even when synthesized using careful, air‐free chemistry techniques and ligands more weakly interacting than those often reported in the literature, the magnetic saturation of iron nanoparticles generally only approaches, but not equals, the magnetic saturation of bulk iron. Here, iron nanoparticles are synthesized using Schlenk line chemistry methods and two different weakly interacting ligands: 2,4‐pentanedione and hexaethylene glycol monododecylether. These particles have saturation magnetizations slightly lower than bulk iron, which is believed to be caused by interactions between the passivating ligands and the surface of the nanoparticles. Using X‐ray absorption fine structure studies, it is shown that oxidized species of iron exist at the nanoparticles’ surface and can be attributed to iron/ligand interaction. The percentage of oxidized species scales with the surface to volume ratio of the nanoparticles, and therefore appears limited to the nanoparticle surface. X‐ray absorption fine structure analysis also shows that the nanoparticles have an expanded crystalline lattice, which can further impact their magnetic properties.     

Nucleation of Polypropylene Crystallization with Gold Nanoparticles. Part 2: Relation between Particle Morphology and Nucleation Activity

The influence of gold nanoparticle morphology on nucleation of isotactic polypropylene (PP) crystallization was investigated. Previous experiments indicated certain nucleation activity of gold nanoparticles, varying with their size. In this work, eight types of gold micro/nanoparticles were used: vacuum-sputtered nanostructures (nanoparticles, nanoislands, and nanolayers), chemically prepared isometric gold nanocrystals (5, 20, and 100 nm diameters), and two types of gold microcrystals with well-developed crystal facets [with (100) and (111) facets, respectively]. To minimize the effect of particle agglomeration, we used our recently introduced sandwich method, in which the nucleating agent was deposited between thin PP films and the nucleation was evaluated by polarized light microscopy (PLM), X-ray scattering (WAXS), and differential scanning calorimetry (DSC). The nucleation activity of Au particles in PP was lower than it might be expected from the previous studies and depended on their morphology. The nucleation activity of Au microcrystals with well-developed facets was higher than the activity of non-faceted Au nanocrystals.     

The Sedimentation of Colloidal Nanoparticles in Solution and Its Study Using Quantitative Digital Photography

Sedimentation and diffusion are important aspects of the behavior of colloidal nanoparticles in solution, and merit attention during the synthesis, characterization, and application of nanoparticles. Here, the sedimentation of nanoparticles is studied quantitatively using digital photography and a simple model based on the Mason–Weaver equation. Good agreement between experimental time‐lapse photography and numerical solutions of the model is found for a series of gold nanoparticles. The new method is extended to study for the first time the gravitational sedimentation of DNA‐linked gold nanoparticle dimers as a model system of a higher complexity structure. Additionally, simple formulas are derived for estimating suitable parameters for the preparative centrifugation of nanoparticle solutions.     

Chip‐Free Microscale‐Incubator‐Based Synthesis of Chitosan‐Based Gene Silencing Nanoparticles

The development of polymer‐based nanoparticles to ferry siRNA continues to evolve. It is becoming increasingly apparent that gene silencing nanoparticles produced by conventional bulk manufacturing techniques often exhibit physicochemical heterogeneity within and between batches that can affect the biological performance. Here a new facile and robust “chip‐free” method is presented, termed chip‐free agitation‐generated droplets (CAD) preparation, using chitosan‐based gene silencing nanoparticles as an example. The CAD‐prepared silencing particles, in comparison to the particles prepared by the conventional bulk protocol, exhibit lower surface charge (9 mV vs 21 mV at N/P = 5), higher stability (≈40% higher binding affinity and up to 30% less morphological deformation), and are less prone to aggregation measured by nanoparticle tracking analysis over a period of one month. Furthermore, these physical attributes contribute up to 19% higher in cell viability at N/P = 5, while the gene silencing of enhanced green fluorescent protein remains constant in a human cell line. Control of particle properties is necessary to advance siRNA‐based delivery; the CAD preparation represents a physical complement to chemical design modifications, which can be readily transferred among research labs and utilized for alternative polymer systems.     

Nucleation of Polypropylene with Gold Nanoparticles. Part 1: Introduction of Sandwich Method for Evaluation of Very Weak Nucleation Activity

Although gold particles are known to nucleate isotactic polypropylene (PP), the nucleating effect of chemically pure 5 nm Au, prepared in vacuum sputter coater, was found to be hardly observable. In order to detect such a weak effect, we deposited a homogeneous layer of Au nanoparticles between thin PP films and evaluated the nucleation activity by a combination of three independent methods: polarized light microscopy (PLM), differential scanning calorimetry (DSC), and 2D wide-angle X-ray scattering (2D-WAXS). This new technique, which was called sandwich method, allowed us to demonstrate that gold nanoparticles were able to nucleate PP crystallization, although the effect was much weaker than that produced by commercial α-nucleant [1,2,3,4-bis(3,4-dimethylbenzylidene)sorbitol] and β-nucleant (N,N-Dicyclohexyl-2,6-naphthalene dicarboxamide). The sandwich method appeared to be quite universal and applicable for any micro-sized nucleants or nanonucleants.     

Anthracene‐Based Colloidal Polymer Nanoparticles: Their Photochemical Ligation and Waterborne Coating Applications

In the current work, a linear polymer, with anthracene moieties in the side chain, is prepared via step‐growth polymerization using epoxide‐amine ring opening reaction. The polymer is dispersed in water to form physically crosslinked nanoparticles (NPs), which are formed by π–π stacking of anthracene moieties. Later, the NPs are crosslinked using UV irradiation, where the anthracene units in the core are simply dimerized and crosslinked the individual chain. In this process, no significant interparticle crosslinking is observed. The higher structural integrity of the chemically crosslinked Nps is revelled via a simple swelling test. The colloidal solution is used to coat glass and silica surfaces homogeneously, which enhances the surface roughness significantly as revealed by atomic force microscope and contact angle measurements.     

Preparation of Ultrafine Colloidal Gold Particles using a Bioactive Molecule

Synthesis of nanometer-sized particles with new physical properties is an area of tremendous interest. In metal particles, the changes in size modify the electron density in the particles, which shifts the plasmon band. The most significant size effects occur when the particles are ultrafine (size is <10 nm). Thus the synthesis of ultrafine metal particles is enormously important to exploit their unique and selective application. Here we report a novel method for the synthesis of ultrafine gold particles in the size range of 0.5–3 nm using dopamine hydrochloride (dhc), an important neurotransmitter. This is the first time where such an important bioactive molecule like dhc has been used as a reagent for the transformation of Au(III) to Au(0). The synthesis is carried out, for the first time, either in simple aqueous or in a nonionic micellar (for example Triton X-100 (TX-100)) medium. The gold sol has a beautiful yellow–brown color showing _max at 470 nm. The appearance of the absorption peak at substantially shorter wavelength (usually gold sol absorbs at 520 nm) indicates that the particles are very small. The method discussed here is very simple, reproducible and does not involve any reagent, which contains 'P' or 'S' atoms. Also in this case no polymer or dendrimer or thiol-related stabilizer is used. The effects of different parameters (such as the presence or absence of O₂, temperature, TX-100 concentration and dhc concentration) on the formation of ultrafine gold particles are discussed. The effects of 3-mercapto propionic acid and pyridine on the ultrafine gold sol are also studied and compared with those on photochemically prepared gold sol. It is observed that 3-mercapto propionic acid dampens the plasmon absorption at 470 nm of ultrafine gold particles. Pyridine, on the other hand, has no effect on the particles.     

Sonochemical Synthesis of Optically Tuneable Conjugated Polymer Nanoparticles

The development of novel and simple methodologies for the obtaining of semiconductive polymer nanoparticles with fine‐tuned optical properties represents nowadays a challenging research area as it involves a simultaneous chemical modification and nanostructuration of the polymer. Here, starting from poly[2‐methoxy‐5‐(2‐ethylhexyloxy)‐1,4‐phenylenevinylene], this objective is achieved with the one‐pot synthesis of oligomers with tunable conjugation length and their nanostructuration, employing a miniemulsion method. Ultrasound irradiation of heterogeneous mixtures leads to the formation of hypochlorous acid that disrupts the electronic conjugation through polymer chain cleavage. Moreover, control over the degree of the electronic conjugation of the oligomers, and therefore of the optical properties, is achieved simply by varying the polymer concentration of the initial solution. Finally, the presence of surfactants during the sonication allows for the formation of nanoparticles with progressive spectral shift of the main absorption (from λ_max = 476 to 306 nm) and emission bands (from λ_max = 597 to 481 nm). The integration of conducting polymer nanoparticles into polymeric matrices yields self‐standing and flexible fluorescent films.     

Blood Compatibility of Multilayered Polyelectrolyte Films Containing Immobilized Gold Nanoparticles

Surface material functionalization including layer‐by‐layer (LbL) polyelectrolyte films with incorporated nanoparticles is a growing field with a wide range of biomedical applications: drug reservoirs, medical devices, or tissue engineering. In parallel, gold nanoparticles (AuNPs) can be grafted by drugs and sensitive molecules using simple protocols. This study shows that AuNP behavior is modified when they are entrapped into three partner LbL films in comparison to the colloidal solution. A polycationic (polyallylamine hydrochloride (PAH)) and a polyanionic (polyacrylic acid (PAA)) polymer is used to build films based on three cycles ((PAH/AuNP/PAA)₃). To investigate the interaction with biomolecules and cells, three different films are developed changing the outer layer (either PAH or AuNP or PAA) with the same number of AuNP deposit. The best biocompatibility is observed with a polyacrylic acid outer layer. Due to the high capacity of drug grafting on gold nanoparticles, the results seem promising for the development of nanostructured biomedical devices.     

Colloidal Core–Satellite Supraparticles via Preprogramed Burst of Nanostructured Micro‐Raspberry Particles

Colloidal molecules, or more general supraparticles, i.e., particles which are themselves assembled of smaller nanoparticles in a defined way, are known to be synthesizable via bottom‐up assembly techniques in colloidal dispersion. The amount of synthesizable particles is mostly limited to milligrams. Herein, a bottom‐up‐programed, triggerable top‐down process is reported to obtain core–satellite supraparticles, i.e., particles composed of a larger core particle surrounded by smaller satellite particles. The key is to prepare a nanostructured, microparticulate powder into which defined burst behavior is preprogramed. Once the system is mechanically triggered, it bursts into well‐defined nanosized core–satellite supraparticles. Scale‐up is easily feasible and several hundred grams per batch can be demonstrated. The product is a ready‐to‐use and flexibly processible powder. Upon simple mixing with a polymer, it disintegrates into the preprogramed core–satellite supraparticles, thus forming a highly sophisticated nanocomposite with the polymer matrix. A pure silica nanoparticle system and a silica–iron oxide nanoparticle hybrid system are presented to demonstrate the versatility of the approach. Enhanced mechanical and unexpected magneto‐optical properties with the particle system are found. The disintegration of the microparticles into individual core–satellite colloidal supraparticles is confirmed via in situ liquid cell transmission electron microscopy.     

Control of Surface Ligand Density on PEGylated Gold Nanoparticles for Optimized Cancer Cell Uptake

Surface chemistry plays a critical role in the solution phase behavior of gold nanoparticles (Au NPs) for applications such as in situ diagnostics and drug delivery. Polyethylene glycol (PEG), a hydrophilic polymer with low immunogenicity, is most commonly used for protecting Au NPs for biomedical applications. The ligand density and molecular weight of PEG on the gold nanoparticle surface are key factors that control the particles’ behavior. Specifically, the total density of PEG ligands gives rise to a transition from a disorganized, deformable polymer “mushroom” orientation to a more rigid “brush” orientation. Here, it is investigated how to rationally control this transition for Au NPs coated with PEG‐SH molecules within the weight range of 0.55 to 5 kDa, and evaluate their subsequent interaction with cancer cells. Several complementary methods are used to evaluate the effect of PEGylation on biologically relevant aspects, including surface ligand density, hydrodynamic size, dispersity, and cellular toxicity. In this work, the optimal synthesis ratios of PEG:Au NPs for achieving stability and maximum dispersity with 0.55, 1, 2, and 5 kDa PEG are determined to be 2500, 700, 500, and 300, respectively. Importantly, ratios that exceed those necessary for maximum dispersion of the Au NPs as determined by UV–vis and DLS are found to be the best ratios for highest cell viability.     

Size‐Dependence of the Melting Temperature of Individual Au Nanoparticles

Nanoparticles have an immense importance in various fields, such as medicine, catalysis, and various technological applications. Nanoparticles exhibit a significant depression in melting point as their size goes below ≈10 nm. However, nanoparticles are frequently used in high temperature applications such as catalysis where temperatures often exceed several 100 degrees which makes it interesting to study not only the melting temperature depression, but also how the melting progresses through the particle. Using high‐resolution transmission electron microscopy, the melting process of gold nanoparticles in the size range of 2–20 nm Au nanoparticles combined with molecular dynamics studies is investigated. A linear dependence of the melting temperature on the inverse particle size is confirmed; electron microscopy imaging reveals that the particles start melting at the surface and the liquid shell formed then rapidly expands to the particle core.     

Gold Nanoparticles Stabilized by Single Tripodal Ligands

In order to coat the entire surface of gold nanoparticles (AuNPs) by a single ligand, tripodal macromolecules comprising benzylic thioethers coordinating to the AuNP surface are synthesized and their abilities to stabilize AuNPs are investigated. Out of the five studied ligands 1 – 5 , the tetraphenylmethane‐based oligomers 4 and 5 display excellent AuNP coating features. Both ligand structures are able to control the dimensions of the AuNPs by stabilizing particles of narrow size distributions during their syntheses (1.05 ± 0.28 nm for Au‐4 , and 1.15 ± 0.34 nm for Au‐5 ). Closer inspection of these AuNPs by transmission electron microscopy and thermogravimetric analyses suggests that single ligands 4 and 5 are able to stabilize entire AuNPs. These particles Au‐4 and Au‐5 are obtained in good yields and display promising thermal stabilities (110 °C for Au‐4 , and 95 °C for Au‐5 ), making them interesting nanoscale inorganic–organic building blocks for further functionalization/processing by wet chemistry.     

Colloidal Flower‐Shaped Iron Oxide Nanoparticles: Synthesis Strategies and Coatings

The assembly of magnetic cores into regular structures may notably influence the properties displayed by a magnetic colloid. Here, key synthesis parameters driving the self‐assembly process capable of organizing colloidal magnetic cores into highly regular and reproducible multi‐core nanoparticles are determined. In addition, a self‐consistent picture that explains the collective magnetic properties exhibited by these complex assemblies is achieved through structural, colloidal, and magnetic means. For this purpose, different strategies to obtain flower‐shaped iron oxide assemblies in the size range 25–100 nm are examined. The routes are based on the partial oxidation of Fe(OH)₂, polyol‐mediated synthesis or the reduction of iron acetylacetonate. The nanoparticles are functionalized either with dextran, citric acid, or alternatively embedded in polystyrene and their long‐term stability is assessed. The core size is measured, calculated, and modeled using both structural and magnetic means, while the Debye model and multi‐core extended model are used to study interparticle interactions. This is the first step toward standardized protocols of synthesis and characterization of flower‐shaped nanoparticles.     

Assembly of Gold Nanoparticles on Gold Nanorods Using Functionalized Poly(N‐isopropylacrylamide) as Polymeric “Glue”

A telechelic thermoresponsive polymer, α‐amino‐ω‐thiol‐poly(N‐isopropylacrylamide) (H₂N‐PNiPAM‐SH), is used as the polymeric glue to assemble gold nanoparticles (AuNPs) around gold nanorods (AuNRs) into a satellite structure. Prepared by reversible addition‐fragmentation chain transfer polymerization followed by hydrazinolysis, H₂N‐PNiPAM‐SH is able to interlink the two types of the gold building blocks with the thiol‐end grafting on AuNRs and the amine‐end coordinating on the AuNP surface. The density of the grafted AuNPs on AuNRs can be tuned by adjusting the molar ratio between AuNPs and AuNRs in the feed. The resulted satellite‐like assembly exhibits unique optical property that was responsive to temperature change.     

Polymerizable Ligands as Stabilizers for Nanoparticles

Monomers bearing functional groups that can get chemisorbed on nanoparticles to form polymerizable monolayers have emerged as an interesting class of stabilizer ligands for various nanoparticles. High‐surface coverage, their ability to modify the properties of underlying nanoparticles, capability to form polymers of different molecular weights and possibility to make structural modifications make them attractive for their use as stabilizer ligands for nanoparticles. Both in situ and post‐synthesis grafting methods for attaching polymerizable ligands to nanoparticles are frequently used. The advantage of grafting polymerizable stabilizer on the surface of nanoparticles is that initially the polymerizable molecule acts as a proper stabilizer for the nanoparticles and later their surface polymerization or co‐polymerization with another suitable monomer can be carried out to generate the desired polymer scaffold around the nanoparticles, which ensures the increased stability of the resulting core‐polymerized shell nanoparticles. This review discusses interesting reports from recent literature on grafting of polymerizable ligands and their polymerization on gold, silver, silica, and iron oxide nanoparticles.