Template-Directed Synthesis of Colloidal Hollow Particles: Mind the Material Used for the Template.

The dissolution of a polymeric solid typically starts with the absorption of solvent molecules, followed by swelling and volume expansion. Only when the extent of swelling reaches a threshold can the polymer chains be disentangled and then dissolved into the solvent. When the polymeric solid is encapsulated in a rigid shell, the swelling process will be impeded. Despite the widespread use of this process, it is rarely discussed in the literature how the polymeric solid is dissolved from the core for the generation of colloidal hollow particles. Recent studies have started to shed light on the mechanistic details involved in the formation of hollow particles through a template-directed process. Depending on the nature of the material used for the template, the removal of the template may involve different mechanisms and pathways, leading to the formation of distinct products. Here, a number of examples are used to illustrate this important phenomenon that is largely neglected in the literature. This article also discusses how the swelling of a polymeric template encapsulated in a rigid shell can be leveraged to fabricate new types of functional colloidal particles.

Transforming Nanofiber Mats into Hierarchical Scaffolds with Graded Changes in Porosity and/or Nanofiber Alignment.

A method for generating hierarchical scaffolds with graded changes in porosity and/or fiber alignment through solution-masked, vapor-induced welding of electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers is reported. The success of this method relies on the fact that the PLGA nanofibers are swollen and welded more slowly by ethanol when immersed in its aqueous solution relative to direct exposure to its vapor. For a mat composed of random nanofibers, the treatment generates a gradation in porosity (both surface and bulk), with the over-welded region evolving from a highly porous mat into a dense film. If uniaxially aligned nanofibers are involved, however, graded changes are observed in both surface porosity and fiber alignment. When bone marrow stem cells are cultured on such a scaffold, they exhibit highly organized and random morphologies on the regions of uniaxially aligned nanofibers and dense film, respectively, with gradual changes in between. Such a scaffold shows promise in mimicking the connective tissue, such as the tendon-to-bone insertion, that relies on a graded transition in cell morphology from uniaxially aligned to random.

Three-Dimensional Objects Consisting of Hierarchically Assembled Nanofibers with Controlled Alignments for Regenerative Medicine.

Assembling electrospun nanofibers with controlled alignment into three-dimensional (3D), complex, and predesigned shapes has proven to be a difficult task for regenerative medicine. Herein, we report a novel approach inspired by solids of revolution that transforms two-dimensional (2D) nanofiber mats of a controlled thickness into once-inaccessible 3D objects with predesigned shapes. The 3D objects are highly porous, consisting of layers of aligned nanofibers separated by gaps ranging from several micrometers to several millimeters. Upon compression, the objects are able to recover their original shapes. The porous objects can serve as scaffolds, guiding the organization of cells and producing highly ordered 3D tissue constructs. Additionally, subcutaneous implantation in rats demonstrates that the 3D objects enable rapid cell penetration, new blood vessel formation, and collagen matrix deposition. This new class of 3D hierarchical nanofiber architectures offers promising advancements in both in vitro engineering of complex 3D tissue constructs/models or organs and in vivo tissue repair and regeneration.

Synthesis of CaO2 Nanocrystals and Their Spherical Aggregates with Uniform Sizes for Use as a Biodegradable Bacteriostatic Agent.

As a solid precursor to O2 and hydrogen peroxide (H2 O2 ), calcium peroxide (CaO2 ) has found widespread use in applications related to disinfection and contaminant degradation. The lack of uniform nanoparticles, however, greatly limits the potential use of this material in other applications related to medicine. Here, a new route to the facile synthesis of CaO2 nanocrystals and their spherical aggregates with uniform, controllable sizes is reported. The synthesis involves the reaction between CaCl2 and H2 O2 to generate CaO2 primary nanocrystals of 2-15 nm in size in ethanol, followed by their aggregation into uniform, spherical particles with the aid of poly(vinyl pyrrolidone) (PVP). The average diameter of the spherical aggregates can be easily tuned in the range of 15-100 nm by varying the concentrations of CaCl2 and/or PVP. For the spherical aggregates with a smaller size, they release H2 O2 and O2 more quickly when exposed to water, resulting in superior antimicrobial activity. This study not only demonstrates a new route to the synthesis of uniform CaO2 nanocrystals and their spherical aggregates but also offers a promising bacteriostatic agent with biodegradability.

Direct Visualization and Semi-Quantitative Analysis of Payload Loading in the Case of Gold Nanocages.

Upon incubation with Au nanocages, pyrrole (Py) molecules can enter the cavities by diffusing through the porous walls and then be polymerized to generate a polypyrrole (PPy) coating on the inner surface. The thicknesses of the PPy coating can serve as a direct indicator for the amount of Py molecules that diffuse into the cavity. Py molecules are able to diffuse into the cavities throughout the polymerization process, while a prolonged incubation time increases the amount of Py accumulated on both inner and outer surfaces of the nanocages. Furthermore, it is demonstrated that the dimensions of the cavity and the size of the pores in the wall are not critical parameters in determining the loading efficiency, as they do not affect the thickness of the PPy coating on the inner surface. These findings offer direct evidence to support the applications of Au nanocages as carriers for drug delivery and controlled release.

Photothermal Welding, Melting, and Patterned Expansion of Nonwoven Mats of Polymer Nanofibers for Biomedical and Printing Applications.

We report a simple method for the photothermal welding of nonwoven mats of electrospun nanofibers by introducing a near-infrared (NIR) dye such as indocyanine green. By leveraging the strong photothermal effect of the dye, the nanofibers can be readily welded at their cross points or even over-welded (i.e., melted and/or fused together) to transform the porous mat into a solid film upon exposure to a NIR laser. While welding at the cross points greatly improves the mechanical strength of a nonwoven mat of nanofibers, melting and fusion of the nanofibers can be employed to fabricate a novel class of photothermal papers for laser writing or printing without chemicals or toner particles. By using a photomask, we can integrate photothermal welding with the gas foaming technique to pattern and then expand nonwoven mats into 3D scaffolds with well-defined structures. This method can be applied to different combinations of polymers and dyes, if they can be co-dissolved in a suitable solvent for electrospinning.

Promoting the Outgrowth of Neurites on Electrospun Microfibers by Functionalization with Electrosprayed Microparticles of Fatty Acids.

Controlling the outgrowth of neurites is important for enhancing the repair of injured nerves and understanding the development of nervous systems. Herein we report a simple strategy for enhancing the outgrowth of neurites through a unique integration of topographical guidance and a chemical cue. We use electrospray to easily functionalize the surface of a substrate with microparticles of natural fatty acids at a controllable density. Through a synergistic effect from the surface roughness arising from the microparticles and the chemical cue offered by the fatty acids, the outgrowth of neurites from PC12 cells is greatly enhanced. We also functionalize the surfaces of uniaxially aligned, electrospun microfibers with the microparticles and further demonstrate that the substrates can guide and enhance directional outgrowth of neurites from both PC12 multicellular spheroids and chick embryonic dorsal root ganglia bodies.

Encapsulation of a Phase-Change Material in Nanocapsules with a Well-Defined Hole in the Wall for the Controlled Release of Drugs.

As a class of biocompatible and biodegradable phase-change materials, natural fatty acids have received considerable interest in recent years for temperature-controlled release of drugs. However, the poor dispersibility and colloidal stability of their nanoparticles under physiological conditions place a major limitation on their applications in biomedicine. Herein, we report a facile method for encapsulating a mixture of two natural fatty acids (with a eutectic melting point at 39 °C) in a biocompatible, silica-based nanocapsule to achieve both stable dispersion and controllable release of drugs. The nanocapsules have a well-defined hole in the wall to ensure easy loading of fatty acids, together with multiple types of functional components such as therapeutics and near-infrared dyes. The payloads can be released through the hole when the fatty acids are melted upon photothermal heating. The release profile can be controlled by varying the size of the hole and/or the duration of laser irradiation.

Melanocortin 1 Receptor Targeted Imaging of Melanoma With Gold Nanocages and Positron Emission Tomography.

PURPOSE: Melanoma is a lethal skin cancer with unmet clinical needs for targeted imaging and therapy. Nanoscale materials conjugated with targeting components have shown great potential to improve tumor delivery efficiency while minimizing undesirable side effects in vivo. Herein, we proposed to develop targeted nanoparticles for melanoma theranostics. METHOD: In this work, gold nanocages (AuNCs) were conjugated with α-melanocyte-stimulating hormone (α-MSH) peptide and radiolabeled with 64Cu for melanocortin 1 receptor-(MC1R) targeted positron emission tomography (PET) in a mouse B16/F10 melanoma model. RESULTS: Their controlled synthesis and surface chemistry enabled well-defined structure and radiolabeling efficiency. In vivo pharmacokinetic evaluation demonstrated comparable organ distribution between the targeted and nontargeted AuNCs. However, micro-PET/computed tomography (CT) imaging demonstrated specific and improved tumor accumulation via MC1R-mediated delivery. By increasing the coverage density of α-MSH peptide on AuNCs, the tumor delivery efficiency was improved. CONCLUSION: The controlled synthesis, sensitive PET imaging, and optimal tumor targeting suggested the potential of targeted AuNCs for melanoma theranostics.

Toward the Synthesis of Sub-15 nm Ag Nanocubes with Sharp Corners and Edges: The Roles of Heterogeneous Nucleation and Surface Capping.

We report a polyol method for the facile synthesis of Ag nanocubes having sharp corners and edges, together with edge lengths below 15 nm. The rapid nucleation of Ag atoms was facilitated through the addition of a trace amount of SH(-) to generate Ag2S clusters while the corners and edges of the nanocubes were sharpened through the introduction of Br(-) as a regulator of the growth kinetics and a capping agent for the Ag(100) surface. Because of their much smaller size relative to the more commonly used capping agent based on poly(vinylpyrrolidone), Br(-) ions are more effective in passivating the {100} facets on very small Ag nanocubes. The mechanistic roles of these additives, along with the effects of their interactions with other species present in the reaction solution, were all systematically investigated. The concentration of SH(-) was found to be a particularly effective parameter for tuning the edge length of the nanocubes. As a result of the understanding gained during the course of this study, Ag nanocubes with uniform edge lengths controllable in the range of 13-23 nm could be reliably produced. The nanocubes of 13.4 ± 0.4 nm in edge length constitute the smallest nanocrystals of this kind reported to date; they also possess sharper corners and edges relative to the limited examples of sub-20 nm Ag nanocubes reported in the literature. The availability of such small and sharp Ag nanocubes will open the door to an array of applications in plasmonics, catalysis, and biomedicine.

Micropatterning of the Ferroelectric Phase in a Poly(vinylidene difluoride) Film by Plasmonic Heating with Gold Nanocages.

Polymer thin films with patterned ferroelectric domains are attractive for a broad range of applications, including the fabrication of tactile sensors, infrared detectors, and non-volatile memories. Herein, we report the use of gold nanocages (AuNCs) as plasmonic nanostructures to induce a ferroelectric-paraelectric phase transition in a poly(vinylidene fluoride) (PVDF) thin film by leveraging its photothermal effect. This technique allows us to generate patterned domains of ferroelectric PVDF within just a few seconds. The incorporation of AuNCs significantly enhances the pyroelectric response of the ferroelectric film under near-infrared irradiation. We also demonstrate the use of such patterned ferroelectric films for near-infrared sensing/imaging.

Protein capsules with cross-linked, semipermeable, and enzyme-degradable surface barriers for controlled release.

This paper describes a method for fabricating protein-based capsules with semipermeable and enzyme-degradable surface barriers. It involves the use of a simple fluidic device to generate water-in-oil emulsion droplets, followed by cross-linking of proteins at the water-oil interface to generate a semipermeable surface barrier. The capsules can be readily fabricated with uniform and controllable sizes and, more importantly, show selective permeability toward molecules with different molecular weights: small molecules like fluorescein sodium salt can freely diffuse through the surface barrier while macromolecules such as proteins can not. The proteins, however, can be released by digesting the surface barrier with an enzyme such as pepsin. Taken together, the capsules hold great potential for applications in controlled release, in particular, for the delivery of protein drugs.

Radioluminescent gold nanocages with controlled radioactivity for real-time in vivo imaging.

Cerenkov luminescence imaging based on light emission from the decay of radionuclides has recently drawn great interest in molecular imaging. In this paper, we report for the first time the Cerenkov luminescence phenomenon of (198)Au isotope, as well as a facile route to the preparation of radioluminescent Au nanocages without additional radiolabeling or dye conjugation. The specific radioactivity of the Au nanocages could be easily and precisely controlled by varying the concentration of H(198)AuCl(4) precursor used for the galvanic replacement reaction. The direct incorporation of (198)Au atoms into the structure of Au nanocages enabled the ability of accurate analysis and real-time imaging in vivo. Furthermore, under biological conditions the radioactive Au nanocages were shown to emit light with wavelengths in the visible and near-infrared regions, enabling luminescence imaging of the whole mice in vivo, as well as the organs ex vivo. When combined with their favorable scattering and absorption properties in the near-infrared region, the radioactive Au nanocages can serve as a new platform for multimodality imaging and will have a significant impact on both small animal and clinical imaging.

Synthesis of rhodium concave tetrahedrons by collectively manipulating the reduction kinetics, facet-selective capping, and surface diffusion.

This paper describes a facile synthesis of Rh tetrahedrons with concave side faces by collectively manipulating the reaction kinetics, facet-selective capping, and surface diffusion of atoms. Specifically, a combination of Na3RhCl6, triethylene glycol, l-ascorbic acid, and citric acid provides the right conditions for generating the concave tetrahedrons. After the formation of small Rh tetrahedral seeds through self-nucleation, the subsequently generated Rh atoms were selectively deposited onto the corner sites to generate Rh tetrapods. At the same time, the deposited atoms could diffuse from the corners to edges to generate concave side faces because the diffusion to face sites was restrained by the citric acid adsorbed on the {111} facets. This study offers deep insight into the growth mechanism involved the formation of noble-metal nanocrystals with concave surfaces. The Rh concave tetrahedrons were encased by a mix of {111} and {110} facets, showing great potential for catalytic applications.

Non-invasive and in situ characterization of the degradation of biomaterial scaffolds by volumetric photoacoustic microscopy.

Degradation is among the most important properties of biomaterial scaffolds, which are indispensable for regenerative medicine. The currently used method relies on the measurement of mass loss across different samples and cannot track the degradation of an individual scaffold in situ. Here we report, for the first time, the use of multiscale photoacoustic microscopy to non-invasively monitor the degradation of an individual scaffold. We could observe alterations to the morphology and structure of a scaffold at high spatial resolution and deep penetration, and more significantly, quantify the degradation of an individual scaffold as a function of time, both in vitro and in vivo. In addition, the remodeling of vasculature inside a scaffold can be visualized simultaneously using a dual-wavelength scanning mode in a label-free manner. This optoacoustic method can be used to monitor the degradation of individual scaffolds, offering a new approach to non-invasively analyze and quantify biomaterial-tissue interactions in conjunction with the assessment of in vivo vascular parameters.

Synthesis of Ag nanocubes 18-32 nm in edge length: the effects of polyol on reduction kinetics, size control, and reproducibility.

This article describes a robust method for the facile synthesis of small Ag nanocubes with edge lengths controlled in the range of 18-32 nm. The success of this new method relies on the substitution of ethylene glycol (EG)--the solvent most commonly used in a polyol synthesis--with diethylene glycol (DEG). Owing to the increase in hydrocarbon chain length, DEG possesses a higher viscosity and a lower reducing power relative to EG. As a result, we were able to achieve a nucleation burst in the early stage to generate a large number of seeds and a relatively slow growth rate thereafter; both factors were critical to the formation of Ag nanocubes with small sizes and in high purity (>95%). The edge length of the Ag nanocubes could be easily tailored in the range of 18-32 nm by quenching the reaction at different time points. For the first time, we were able to produce uniform sub-20 nm Ag nanocubes in a hydrophilic medium and on a scale of ∼20 mg per batch. It is also worth pointing out that the present protocol was remarkably robust, showing good reproducibility between different batches and even for DEGs obtained from different vendors. Our results suggest that the high sensitivity of synthesis outcomes to the trace amounts of impurities in a polyol, a major issue for reproducibility and scale up synthesis, did not exist in the present system.

Robust synthesis of gold cubic nanoframes through a combination of galvanic replacement, gold deposition, and silver dealloying.

A facile, robust approach to the synthesis of Au cubic nanoframes is described. The synthesis involves three major steps: 1) preparation of Au-Ag alloyed nanocages using a galvanic replacement reaction between Ag nanocubes and HAuCl4 ; 2) deposition of thin layers of pure Au onto the surfaces of the nanocages by reducing HAuCl4 with ascorbic acid, and; 3) formation of Au cubic nanoframes through a dealloying process with HAuCl4 . The key to the formation of Au cubic nanoframes is to coat the surfaces of the Au-Ag nanocages with sufficiently thick layers of Au before they are dealloyed. The Au layer could prevent the skeleton of a nanocage from being fragmented during the dealloying step. The as-prepared Au cubic nanoframes exhibit tunable localized surface plasmon resonance peaks in the near-infrared region, but with much lower Ag content as compared with the initial Au-Ag nanocages.

Maneuvering the internal porosity and surface morphology of electrospun polystyrene yarns by controlling the solvent and relative humidity.

This article presents a simple and reliable method for generating polystyrene (PS) yarns composed of bundles of nanofibrils by using a proper combination of solvent and relative humidity. We elucidated the mechanism responsible for the formation of this new morphology by systematically investigating the molecular interactions among the polymer, solvent(s), and water vapor. We demonstrated that vapor-induced phase separation played a pivotal role in generating the yarns with a unique structure. Furthermore, we discovered that the low vapor pressure of N,N-dimethylformamide (DMF) was critical to the evolution of pores in the interiors. On the contrary, the relatively high vapor pressure of tetrahydrofuran (THF) hindered the formation of interior pores but excelled in creating a rough surface. In all cases, our results clearly indicate that the formation of either internal porosity or surface roughness required the presence of water vapor, a nonsolvent of the polymer, at a proper level of relative humidity. The exact morphology or pore structure was dependent on the speed of evaporation of the solvent(s) (DMF, THF, and their mixtures) as well as the interdiffusion and penetration of the nonsolvent (water) and solvent(s). Our findings can serve as guidelines for the preparation of fibers with desired porosity both internally and externally through electrospinning.

Controlling the pore sizes and related properties of inverse opal scaffolds for tissue engineering applications.

Inverse opal scaffolds are finding widespread use in tissue engineering and regenerative medicine. Herein, the way in which the pore sizes and related physical properties of poly(D,L-lactide-co-glycolide) inverse opal scaffolds are affected by the fabrication conditions is systematically investigated. It is found that the window size of an inverse opal scaffold is mainly determined by the annealing temperature rather than the duration of time, and the surface pore size is largely determined by the concentration of the infiltration solution. Although scaffolds with larger pore or window sizes facilitate faster migration of cells, they show slightly lower compressive moduli than scaffolds with smaller pore or window sizes.

Symmetry breaking during seeded growth of nanocrystals.

Currently, most of the reported noble-metal nanocrystals are limited to a high level of symmetry, as constrained by the inherent, face-centered cubic (fcc) lattice of these metals. In this paper, we report, for the first time, a facile and versatile approach (backed up by a clear mechanistic understanding) for breaking the symmetry of an fcc lattice and thus obtaining nanocrystals with highly unsymmetrical shapes. The key strategy is to induce and direct the growth of nanocrystal seeds into unsymmetrical modes by manipulating the reduction kinetics. With silver as an example, we demonstrated that the diversity of possible shapes taken by noble-metal nanocrystals could be greatly expanded by incorporating a series of new shapes drastically deviated from the fcc lattice. This work provides a new method to investigate shape-controlled synthesis of metal nanocrystal.