Nanostructured Lipid‐Based Films for Substrate‐Mediated Applications in Biotechnology

Amphiphilic in nature, lipids spontaneously self‐assemble into a range of nanostructures in the presence of water. Among lipid self‐assembled structures, liposomes and supported lipid bilayers have long held scientific interest for their main applications in drug delivery and plasma membrane models, respectively. In contrast, lipid‐based multilayered membranes on solid supports only recently begin drawing scientists' attention. Current studies show that the stacking of multiple bilayers on a solid support yields cooperative structural and dynamic behavior that enables new functionalities. Lipid films provide compartmentalization, templating, and enhanced release of molecules of interest. Importantly, supported lipid phases exhibit long‐range periodic nanoscale order and orientation that is tunable in response to a changing environment. Herein, the current understanding of lipid‐based film research is summarized focusing on how unique structural characteristics enable the emergence of new applications including label‐free biosensors, macroscale drug delivery, and substrate‐mediated gene delivery. The authors' recent contributions focusing on the structural characterization of lipid‐based films using small‐angle X‐ray scattering and atomic force microscopy are highlighted. In addition, new photothermally induced resonance and solid‐state nuclear magnetic resonance data are described, providing insights into drug partition in lipid‐based films as well as structure and dynamics at the molecular scale.     

Hierarchical Directed Self‐Assembly of Diblock Copolymers for Modified Pattern Symmetry

Block copolymer lithography exploiting diblock copolymer thin films is promising for scalable manufacture of device‐oriented nanostructures. Nonetheless, its intrinsic limitation in the degree of freedom for pattern symmetry within hexagonal dot or parallel line array greatly diminishes the potential application fields. Here, we report multi‐level hierarchical self‐assembled nanopatterning of diblock copolymers for modified pattern symmetry. Sequential hierarchical integration of two layers of diblock copolymer films with judiciously chosen molecular weights and chemical composition creates nanopatterned morphology with modified pattern symmetry, including sparse linear cylinder or lamellar arrays. Internal structure of the hierarchically patterned morphology is characterized by grazing‐incidence small‐angle X‐ray scattering throughout the film thickness. Pattern transfer of the modified nanopattern generates linear metal nanodot array with uniform size and regular spacing as a typical example of functional nanopatterned structures.     

A Fabricated siRNA Nanoparticle for Ultralong Gene Silencing In Vivo

Persistent gene silencing is crucially required for the successful therapeutics of short interfering RNA (siRNA). Here, a nanoparticle‐based delivery system is presented which assembles by layering siRNAs between protease degradable polypeptides to extend the therapeutic window. These tightly packed nanoparticles are efficiently taken up by cells by endocytosis, and the fabricated siRNAs are gradually released following intracellular degradation of the polypeptide layers. During cell division, the particles are distributed to the daughter cells. Due to the slow degradation through the multiple layers, the particles continuously release siRNA in all cells. Using this controlled release construct, the in vivo gene silencing effect of siRNA is consistent for an ultralong period of time (>3 weeks) with only a single treatment.     

IL4‐Receptor‐Targeted Dual Antitumoral Apoptotic Peptide—siRNA Conjugate Lipoplexes

Targeted delivery remains the major limitation in the development of small interfering RNA (siRNA) therapeutics. The successful siRNA multistep delivery requires precise carriers of substantial complexity. To achieve this, a monodisperse carrier is presented, synthesized by solid‐phase supported chemistry. The sequence‐defined assembly contains two oleic acids attached to a cationizable oligoaminoamide backbone in T‐shape configuration, and a terminal azide functionality for coupling to the atherosclerotic plaque‐specific peptide‐1 (AP‐1) as the cell targeting ligand for interleukin‐4 receptor (IL‐4R) which is overexpressed in a variety of solid cancers. For combined cytosolic delivery with siRNA, different apoptotic peptides (KLK, BAK, and BAD) are covalently conjugated via bioreversible disulfide linkage to the 5′‐end of the siRNA sense strand. siRNA‐KLK conjugates provide the highest antitumoral potency. The optimized targeted carrier is complexed with dual antitumoral siEG5‐KLK conjugates. The functionality of each subdomain is individually confirmed. The lipo‐oligomer confers stable assembly of siRNA conjugates into spherical 150–250 nm sized nanoparticles. Click‐shielding with dibenzocyclootyne‐PEG‐AP‐1 (DBCO‐PEG‐AP‐1) mediates an IL‐4R‐specific cell targeting and gene silencing in tumor cells. Most importantly, formulation of the siEG5‐KLK conjugate displays enhanced apoptotic tumor cell killing due to the combined effect of mitotic arrest by EG5 gene silencing and mitochondrial membrane disruption by KLK.     

Profile Control in Block Copolymer Nanostructures using Bilayer Thin Films for Enhanced Pattern Transfer Processes

Although control over the domain orientation and long‐range order of block copolymer nanostructures self‐assembled in thin films has been achieved using various directed self‐assembly techniques, more challenging but equally important for many lithographic applications is the ability to precisely control the shape of the interface between domains. Here, a novel layer‐by‐layer approach is reported for controlling the interface profile of block copolymer nanostructures and the application of an undercut sidewall profile for an enhanced metal lift‐off process for pattern transfer is demonstrated. Bilayer films of lamellar‐forming poly(styrene‐block‐methyl methacrylate) are assembled and thermally cross‐linked on wafer substrates in a layer‐by‐layer process. The top layer, while being directed to self‐assemble on the lamellae of the underlying layer, has a tunable composition and polystyrene domain width independent of that of the bottom layer. Undercut or negative sidewall profiles in the PS nanostructures are proven to provide better templates for the lift‐off of Au nanowires by achieving complete and defect‐free pattern transfer more than three times faster than comparable systems with vertical sidewall profiles. More broadly, the layer‐by‐layer approach presented here provides a pathway to achieving sophisticated interface profiles and user‐defined 3D block copolymer nanostructures in thin films.     

立方GaAs（100）衬底上制备单相六方GaN薄膜

立方GaAs（100）衬底上制备的GaN薄膜多为立方结构且立方相为亚稳相,采用水平常压MOCVD方法在立方GaAs（100）衬底上制备出了GaN薄膜．XRD测试表明,薄膜具有单一的相．结合对工艺条件的分析,认为薄膜具有六方结构．最后,通过Raman光谱测试,证实在立方GaAs衬底上制备出了单相六方GaN薄膜．还对立方GaAs衬底上制备出六方GaN薄膜的原因进行了讨论．     

Nano‐Self‐Assembly of Nucleic Acids Capable of Transfection without a Gene Carrier

Nonviral gene carriers based on electrostatic interaction, encapsulation, or absorption require a large amount of polymer carrier to achieve reasonable transfection efficiencies. With cationic nanoparticles, for example, genes interact only with the surface of the nanoparticles, resulting in a low surface area to volume ratio (SA/V = 3/r). A large volume of carrier, therefore, is required to deliver a small copy number of genes. In this study, it is demonstrated that a nano‐self‐assembly of nucleic acids transfects itself into cells spontaneously, without the need for a gene carrier. The cellular uptake of this nanoassembly occurs through a number of endocytosis mechanisms. Once within the cell, the nanoassembly can escape endolysosomal vesicles and facilitate gene transfection. This nano‐self‐assembly consisting of zinc and plasmid DNA or siRNA, termed the Zn/DNA or Zn/siRNA nanocluster, is formed through the binding of Zn²⁺ ions to the phosphate groups of nucleic acids. The method described in this paper represents a new platform for carrier‐free gene delivery that can be used to deliver any plasmid DNA or siRNA without the requirement for a specific modification in the nucleic acids or complicated steps to prepare dense particles.     

Large‐Area,Periodic, Hexagonal Wrinkles on Nanocrystalline Graphitic Film

Sinusoidal wrinkles develop in compressively stressed film as a means to release stored elastic energy. Here, a simple way to fabricate large‐area, periodic, hexagonal wrinkled pattern on nanocrystalline graphitic films grown on c‐plane sapphire (<50 nm thick) by the spontaneous delamination–buckling of the as‐grown film during cooling is reported. According to the continuum mechanics calculation, strain‐relief pattern adopting the hexagonal wrinkled pattern has a lower elastic energy than that of the telephone cord wrinkle at thickness regime below 50 nm. A high‐fidelity transfer method is developed to transfer the hexagonal wrinkled films onto arbitrary substrates. Nanoindentation studies show that hexagonal wrinkle film engineered this way may act as shock absorber. The hexagonal wrinkled carbon film is able to selectively promote the differentiation of human mesenchymal stem cell toward the osteogenic lineage in the absence of osteogenic inducing medium.     

CdS薄膜的结构特性及其对Cu(In,Ga)Se2(CIGS)薄膜太阳电池的影响

报道了CdS薄膜的CBD法沉积及其结构特性,其中的水浴溶液包括硫脲、乙酸镉、乙酸铵和氨水溶液.研究了水浴溶液的pH值、温度、各反应物溶液的浓度和滴定硫脲与倾倒硫脲等基本工艺参数对CdS薄膜结构特性的影响.其中,溶液的pH值对CdS薄膜的特性起着关键的作用.XRD图显示了随着溶液pH值的变化,薄膜的晶相由六方相向立方相转变.CdS薄膜的这两种晶相对CIGS薄膜太阳电池性能的影响不相同.c-CdS(立方相的CdS)与CIGS之间的晶格失配和界面态密度分别为1.419%和8.507×1012cm-2,而h-CdS(六方相的CdS)与CIGS之间的晶格失配和界面态密度则分别为32.297%和2.792×1012cm-2.高效CIGS薄膜太阳电池需要的是立方相CdS薄膜.     

Engineered Proteinticles for Targeted Delivery of siRNA to Cancer Cells

Considering the problems of small interfering RNA (siRNA) delivery using traditional viral and nonviral vehicles, a new siRNA delivery system to enhance efficiency and safety needs to be developed. Here human ferritin‐based proteinticles are genetically engineered to simultaneously display various functional peptides on the surface of proteinticles: cationic peptide to capture siRNA, tumor cell targeting and penetrating peptides, and enzymatically cleaved peptide to release siRNA inside tumor cell. In the in vitro treatment of poly‐siRNA‐proteinticle complex, both of the tumor cell targeting and penetrating peptides are important for efficient delivery of siRNA, and the red fluorescent protein (RFP) expression in RFP‐expressing tumor cells is notably suppressed by the delivered siRNA with the complementary sequence to RFP mRNA. It seems that the human ferritin‐based proteinticle is an efficient, stable, and safe tool for siRNA delivery, having a great potential for application to in vivo cancer treatment. The unique feature of proteinticles is that multiple and functional peptides can be simultaneously and evenly placed and also easily switched on the proteinticle surface through a simple genetic modification, which is likely to make proteinticles appropriate for targeted delivery of siRNA to a wide range of cancer cells.     

溶液PH值对CdS薄膜结构特性的影响

采用化学水浴沉积(CBD)工艺在玻璃衬底上制 备CdS薄膜,研究溶液PH值对CdS 薄膜结构特性的影响。薄膜的厚度、组份、晶相结构和表观形貌分别由台阶仪、X射线荧光 光谱(XRF)、X射线衍射(XRD)和场发射扫描电子显微镜(FESEM)来表征。溶液的 PH值为11.26、 11.37和11.48时,CdS薄膜的晶相以六方相为主,薄膜的厚度先增大后减小; PH值为11.62、11.66时,薄膜的晶相以立方相为主,薄 膜的厚度进一步减小。同时,随着溶液PH值 增大,CdS薄膜的晶格常数也逐渐增大。两种晶相的CdS薄膜缓冲层与CIGS薄膜分别构成异 质 对形成异质结时的晶格失配分别为32.297%和1.419%,界面态密度分别为2.792×10¹⁴和8.507×10¹²,因此高效CIGS薄 膜太阳电池更需要立方相的CdS薄膜。     

Widely Tunable Morphologies in Block Copolymer Thin Films Through Solvent Vapor Annealing Using Mixtures of Selective Solvents

Thin films of block copolymers are extremely attractive for nanofabrication because of their ability to form uniform and periodic nanoscale structures by microphase separation. One shortcoming of this approach is that to date the design of a desired equilibrium structure requires synthesis of a block copolymer de novo within the corresponding volume ratio of the blocks. In this work, solvent vapor annealing in supported thin films of poly(2‐hydroxyethyl methacrylate)‐block‐poly(methyl methacrylate) [PHEMA‐b‐PMMA] by means of grazing incidence small angle X‐ray scattering (GISAXS) is investigated. A spin‐coated thin film of a lamellar block copolymer is solvent vapor annealed to induce microphase separation and improve the long‐range order of the self‐assembled pattern. Annealing in a mixture of solvent vapors using a controlled volume ratio of solvents, which are chosen to be preferential for each block, enables selective formation of ordered lamellae, gyroid, hexagonal, or spherical morphologies from a single‐block copolymer with a fixed volume fraction. The selected microstructure is then kinetically trapped in the dry film by rapid drying. This paper describes what is thought to be the first reported case where in situ methods are used to study the transition of block copolymer films from one initial disordered morphology to four different ordered morphologies, covering much of the theoretical diblock copolymer phase diagram.     

A Fluorinated Bola‐Amphiphilic Dendrimer for On‐Demand Delivery of siRNA,via Specific Response to Reactive Oxygen Species

Functional materials capable of responding to stimuli intrinsic to diseases are extremely important for specific drug delivery at the disease site. However, developing on‐demand stimulus‐responsive vectors for targeted delivery is highly challenging. Here, a stimulus‐responsive fluorinated bola‐amphiphilic dendrimer is reported for on‐demand delivery of small interfering RNA (siRNA) in response to the characteristic high level of reactive oxygen species (ROS) in cancer cells. This dendrimer bears a ROS‐sensitive thioacetal in the hydrophobic core and positively charged poly(amidoamine) dendrons at the terminals, capable of interacting and compacting the negatively charged siRNA into nanoparticles to protect the siRNA and promote cellular uptake. The ROS‐sensitive feature of this dendrimer boosts specific and efficient disassembly of the siRNA/vector complexes in ROS‐rich cancer cells for effective siRNA delivery and gene silencing. Moreover, the fluorine tags in the vector enable ¹⁹F‐NMR analysis of the ROS‐responsive delivery process. In addition, this ingenious and distinct bola‐amphiphilic dendrimer is also able to combine the advantageous delivery features of both lipid and dendrimer vectors. Therefore, it represents an innovative on‐demand stimulus‐responsive delivery platform.     

Novel Direct Nanopatterning Approach to Fabricate Periodically Nanostructured Perovskite for Optoelectronic Applications

While indirectly patterned organic–inorganic hybrid perovskite nanostructures have been extensively studied for use in perovskite optoelectronic devices, it is still challenging to directly pattern perovskite thin films because perovskite is very sensitive to polar solvents and high‐temperature environments. Here, a simple and low‐cost approach is proposed to directly pattern perovskite solid‐state films into periodic nanostructures. The approach is basically perovskite recrystallization through phase transformation with the presence of a periodic mold on an as‐prepared solid‐state perovskite film. Interestingly, this study simultaneously achieves not only periodically patterned perovskite nanostructures but also better crystallized perovskites and improved optical properties, as compared to its thin film counterpart. The improved optical properties can be attributed to the light extraction and increased spontaneous emission rate of perovskite gratings. By fabricating light‐emitting diodes using the periodic perovskite nanostructure as the emission layers, approximately twofold higher radiance and lower threshold than the reference planar devices are achieved. This work opens up a new and simple way to fabricate highly crystalline and large‐area perovskite periodic nanostructures for low‐cost production of high‐performance optoelectronic devices.     

Reductively Dissociable siRNA‐Polymer Hybrid Nanogels for Efficient Targeted Gene Silencing

A highly efficient approach for target‐specific gene silencing based on a reductively dissociable nanogel incorporating small interfering RNA (siRNA) crosslinked with linear polyethylenimine (LPEI) via disulfide bonds is presented. Thiol‐terminated siRNA at both 3′‐ends is electrostatically complexed with thiol‐grafted LPEI. The prepared siRNA/LPEI complex contains inter‐ and intramolecular linkages, generating a mutually crosslinked siRNA/LPEI nanogel (MCN) that exhibits excellent structural stability against the addition of heparin but is readily disintegrated to biologically active, monomeric siRNA upon exposure to reductive conditions. Accordingly, the highly condensed, stable MCN shows greatly enhanced cellular uptake and gene silencing efficiency compared to the siRNA/LPEI complexes without crosslinks or with only LPEI‐mediated crosslinks.     

3D Hexagonal (R‐3m) Mesostructured Nanocrystalline Titania Thin Films: Synthesis and Characterization

A straightforward and reproducible synthesis of crack‐free large‐area thin films of 3D hexagonal (R‐3m) mesostructured nanocrystalline titania (meso‐nc‐TiO₂) using a Pluronic triblock copolymer (P123)/1‐butanol templating system is described. The characterization of the films is achieved using a combination of electron microscopy (high‐resolution scanning electron microscopy and scanning transmission electron microscopy), grazing‐incidence small‐angle X‐ray scattering, in situ high‐temperature X‐ray diffraction, and variable‐angle spectroscopic ellipsometry. The mesostructure of the obtained films is found to be based upon a 3D periodic array of large elliptically shaped cages with diameters around 20 nm interconnected by windows of about 5 nm in size. The mesopores of the film calcined at 300 °C are very highly ordered, and the titania framework of the film has a crystallinity of 40 % being composed of 5.8 nm sized anatase crystallites. The film displays high thermal stability in that the collapse of the pore architecture is incomplete even at 600 °C. The accessible surface area of 3D hexagonal meso‐nc‐TiO₂ estimated by the absorption of methylene blue is nearly twice as large as that of 2D hexagonal meso‐nc‐TiO₂ at the same annealing temperature.     

Humidity‐Triggered Self‐Healing of Microporous Polyelectrolyte Multilayer Coatings for Hydrophobic Drug Delivery

Layer‐by‐layer (LbL) self‐assemblies have inherent potential as dynamic coatings because of the sensitivity of their building blocks to external stimuli. Here, humidity serves as a feasible trigger to activate the self‐healing of a microporous polyethylenimine/poly(acrylic acid) multilayer film. Microporous structures within the polyelectrolyte multilayer (PEM) film are created by acid treatment, followed by freeze‐drying to remove water. The self‐healing of these micropores can be triggered at 100% relative humidity, under which condition the mobility of the polyelectrolytes is activated. Based on this, a facile and versatile method is suggested for directly integrating hydrophobic drugs into PEM films for surface‐mediated drug delivery. The high porosity of microporous film enables the highest loading (≈303.5 μg cm^?2 for a 15‐bilayered film) of triclosan to be a one‐shot process via wicking action and subsequent solvent removal, thus dramatically streamlining the processes and reducing complexities compared to the existing LbL strategies. The self‐healing of a drug‐loaded microporous PEM film significantly reduces the diffusion coefficient of triclosan, which is favorable for the long‐term sustained release of the drug. The dynamic properties of this polymeric coating provide great potential for its use as a delivery platform for hydrophobic drugs in a wide variety of biomedical applications.     

Molecular Gelation‐Induced Functional Phase Separation in Polymer Film for Energy Transfer Spectral Conversion

A new strategy for creating the energy transfer spectral conversion thin film by using fluorophore‐functionalized molecular gelation is proposed. This is based on the facts that nanofibrillar phase separation of the self‐assembling pyrene derivative as a fluorophore is formed in a bulk polymer‐containing organic gel, and consequently that the phase‐separated nano domain in a polymer thin film is enough small to keep the transparency but also extremely high Storks shift is gained by efficient excimer formation through highly ordered stacking among the pyrene moieties. When the phase separation‐mediated functional polymer is applied as spectral conversion films (SCFs) for copper–indium–gallium–selenide (CIGS) solar cell, the SCF‐covered solar cell exhibits significant improvement of power conversion efficiency by increase of photocurrent. In this paper, the FRET efficiency and emission wavelength are also demonstrated to be thermotropically switchable since order‐to‐disordered transitions are essential characteristics of as non‐covalent low molecular assembling.     

Binary Targeting of siRNA to Hematologic Cancer Cells In Vivo Using Layer‐by‐Layer Nanoparticles

Using siRNA therapeutics to treat hematologic malignancies has been unsuccessful because blood cancer cells exhibit remarkable resistance to standard transfection methods. Herein, the successful delivery of siRNA therapeutics with a dual‐targeted, layer‐by‐layer nanoparticle (LbL‐NP) is reported. The LbL‐NP protects siRNA from nucleases in the bloodstream by embedding it within polyelectrolyte layers that coat a polymeric core. The outermost layer consists of hyaluronic acid (a CD44‐ligand) covalently conjugated to CD20 antibodies. The CD20/CD44 dual‐targeting outer layer provides precise binding to blood cancer cells, followed by receptor‐mediated endocytosis of the LbL‐NP. This siRNA delivery platform is used to silence B‐cell lymphoma 2 (BCL‐2), a pro‐survival protein, in vitro and in vivo. The dual‐targeting approach significantly enhances internalization of BCL‐2 siRNA in lymphoma and leukemia cells, which leads to significant downregulation of BCL‐2 expression. Systemic administration of the dual‐targeted, siRNA‐loaded nanoparticle induces apoptosis and hampers proliferation of blood cancer cells, both in cell culture and in orthotopic non‐Hodgkin's lymphoma animal models. These results provide the basis for approaches to targeting blood‐borne cancers and other diseases and suggest that LbL nanoassemblies are a promising approach for delivering therapeutic siRNA to hematopoetic cell types that are known to evade transfection by other means.     

Charge Transportation and Chirality in Liquid Crystalline Helical Network Phases of Achiral BTBT-Derived Polycatenar Molecules

First examples of multichain (polycatenar) compounds, based on the π-conjugated [1]benzothieno[3,2-b]benzothiophene unit are designed, synthesized, and their soft self-assembly and charge carrier mobility are investigated. These compounds, terminated by the new fan-shaped 2-brominated 3,4,5-trialkoxybenzoate moiety, form bicontinuous cubic liquid crystalline (LC) phases with helical network structure over extremely wide temperature ranges (>200 K), including ambient temperature. Compounds with short chains show an achiral cubic phase with the double network, which upon increasing the chain length, is at first replaced by a tetragonal 3D phase and then by a mirror symmetry is broken triple network cubic phase. In the networks, the capability of bypassing defects provides enhanced charge carrier mobility compared to imperfectly aligned columnar phases, and the charge transportation is non-dispersive, as only rarely observed for LC materials. At the transition to a semicrystalline helical network phase, the conductivity is further enhanced by almost one order of magnitude. In addition, a mirror symmetry broken isotropic liquid phase is formed beside the 3D phases, which upon chain elongation is removed and replaced by a hexagonal columnar LC phase.