Multifunctional Core/Shell Nanoparticles Self‐Assembled from pH‐Induced Thermosensitive Polymers for Targeted Intracellular Anticancer Drug Delivery

Core/shell nanoparticles that display a pH‐sensitive thermal response, self‐assembled from the amphiphilic tercopolymer, poly(N‐isopropylacrylamide‐co‐N,N‐dimethylacrylamide‐co‐10‐undecenoic acid) (P(NIPAAm‐co‐DMAAm‐co‐UA)), have recently been reported. In this study, folic acid is conjugated to the hydrophilic segment of the polymer through the free amine group (for targeting cancer cells that overexpress folate receptors) and cholesterol is grafted to the hydrophobic segment of the polymer. This polymer also self‐assembles into core/shell nanoparticles that exhibit pH‐induced temperature sensitivity, but they possess a more stable hydrophobic core than the original polymer P(NIPAAm‐co‐DMAAm‐co‐UA) and a shell containing folate molecules. An anticancer drug, doxorubicin (DOX), is encapsulated into the nanoparticles. DOX release is also pH‐dependent. DOX molecules delivered by P(NIPAAm‐co‐DMAAm‐co‐UA) and folate‐conjugated P(NIPAAm‐co‐DMAAm‐co‐UA)‐g‐cholesterol nanoparticles enter the nucleus more rapidly than those transported by P(NIPAAm‐co‐DMAAm)‐b‐poly(lactide‐co‐glycolide) nanoparticles, which are not pH sensitive. More importantly, these nanoparticles can recognize folate‐receptor‐expressing cancer cells. Compared to the nanoparticles without folate, the DOX‐loaded nanoparticles with folate yield a greater cellular uptake because of the folate‐receptor‐mediated endocytosis process, and, thus, higher cytotoxicity results. These multifunctional polymer core/shell nanoparticles may make a promising carrier to target drugs to cancer cells and release the drug molecules to the cytoplasm inside the cells.     

Molecular Engineering of “Click”‐Phospholes Towards Self‐Assembled Luminescent Soft Materials

Inspired by the self‐assembled bilayer structures of natural amphiphilic phospholipids, a new class of highly luminescent “click”‐phospholes with exocyclic alkynyl group at the phosphorus center is reported. These molecules can be easily functionalized with a self‐assembly group to generate neutral “phosphole‐lipids”. This novel approach retains the versatile reactivity of the phosphorus center, allowing further engineering of the photophysical and self‐assembly properties of the materials at a molecular level. The results of this study highlight the importance of being able to balance weak intermolecular interactions for controlling the self‐assembly properties of soft materials. Only molecules with the appropriate set of intermolecular arrangement/interactions show both organogel and liquid crystal mesophases with well‐ordered microstructures. Moreover, an efficient energy transfer of the luminescent materials is demonstrated and applied in the detection of organic solvent vapors.     

Dramatic Activity of C3N4/BiPO4 Photocatalyst with Core/Shell Structure Formed by Self‐Assembly

Core/shell structured C₃N₄/BiPO₄ photocatalyst is fabricated via a facile ultrasonic dispersion method. The thickness of the shell may be controlled by tuning the amount of C₃N₄ in the dispersion, which determines the enhanced level of photocatalytic activity. The optimum photocatalytic activity of C₃N₄/BiPO₄ at a weight ratio of 4% (C₃N₄/BiPO₄) under UV irradiation is almost 4.5 times as high as that of reference P25 (TiO₂) and 2.5 times of BiPO₄. More attractively, the dramatic visible light photocatalytic activity is generated due to the C₃N₄ loaded. The enhancement in performance is demonstrated to be the match of lattice and energy level between the C₃N₄ and BiPO₄. This match facilitates the separation and transfer of photogenerated electron–hole pairs at the heterojunction interfaces and may be important for other core/shell structured materials. In addition, this method is expected to be extended for other C₃N₄ loaded materials.     

Self‐Assembled Heteroepitaxial Oxide Nanocomposite Thin Film Structures: Designing Interface‐Induced Functionality in Electronic Materials

Achieving self‐assembling/self‐organizing systems is the holy grail of nanotechnology. Spontaneous organization is not unique to the physical sciences since nature has been producing such systems for millions of years. In biological systems global patterns emerge from numerous interactions among lower‐level components of the system. The same is true for physical systems. In this review, the self‐assembly mechanisms of oxide nanocomposite films, as well as the advantageous functionalities that arise from such ordered structures, are explored.     

Kirigami‐Inspired Self‐Assembly of 3D Structures

Self‐assembly of 3D structures presents an attractive and scalable route to realize reconfigurable and functionally capable mesoscale devices without human intervention. A common approach for achieving this is to utilize stimuli‐responsive folding of hinged structures, which requires the integration of different materials and/or geometric arrangements along the hinges. It is demonstrated that the inclusion of Kirigami cuts in planar, hingeless bilayer thin sheets can be used to produce complex 3D shapes in an on‐demand manner. Nonlinear finite element models are developed to elucidate the mechanics of shape morphing in bilayer thin sheets and verify the predictions through swelling experiments of planar, millimeter‐scaled PDMS (polydimethylsiloxane) bilayers in organic solvents. Building upon the mechanistic understandings, The transformation of Kirigami‐cut simple bilayers into 3D shapes such as letters from the Roman alphabet (to make “ADVANCED FUNCTIONAL MATERIALS”) and open/closed polyhedral architectures is experimentally demonstrated. A possible application of the bilayers as tether‐less optical metamaterials with dynamically tunable light transmission and reflection behaviors is also shown. As the proposed mechanistic design principles could be applied to a variety of materials, this research broadly contributes toward the development of smart, tetherless, and reconfigurable multifunctional systems.     

pH‐Responsive Peptide Mimic Shell Cross‐Linked Magnetic Nanocarriers for Combination Therapy

The design and development of water dispersible, pH responsive peptide mimic shell cross‐linked magnetic nanocarriers (PMNCs) using a facile soft‐chemical approach is reported. These nanocarriers have an average size about 10 nm, are resistant to protein adsorption in physiological medium, and transform from a negatively charged to a positively charged form in the acidic environment. The terminal amino acid on the shell of the magnetic nanocarriers allows us to create functionalized exteriors with high densities of organic moieties (both amine and carboxyl) for conjugation of drug molecules. The drug‐loading efficiency of the nanocarriers is investigated using doxorubicin hydrochloride (DOX) as a model drug to evaluate their potential as a carrier system. Results show high loading affinity of nanocarriers for anticancer drug, their sustained release profile, magnetic‐field‐induced heating, and substantial cellular internalization. Moreover, the enhanced toxicity to tumor cells by DOX‐loaded PMNCs (DOX‐PMNCs) under an AC magntic field suggest their potential for combination therapy involving hyperthermia and chemotherapy.     

Reinforcement of Shear Thinning Protein Hydrogels by Responsive Block Copolymer Self‐Assembly

Shear thinning hydrogels are promising materials that exhibit rapid self‐healing following the cessation of shear, making them attractive for applications including injectable biomaterials. Here, self‐assembly is demonstrated as a strategy to introduce a reinforcing network within shear thinning artificially engineered protein gels, enabling a responsive transition from an injectable state at low temperatures with a low yield stress to a stiffened state at physiological temperatures with resistance to shear thinning, higher toughness, and reduced erosion rates and creep compliance. Protein‐polymer triblock copolymers capable of the responsive self‐assembly of two orthogonal networks are synthesized. Midblock association forms a shear‐thinning network, while endblock aggregation at elevated temperatures introduces a second, independent physical network into the protein hydrogel. These reversible crosslinks introduce extremely long relaxation times and lead to a five‐fold increase in the elastic modulus, significantly larger than is expected from transient network theory. Thermoresponsive reinforcement reduces the high temperature creep compliance by over four orders of magnitude, decreases the erosion rate by at least a factor of five, and increases the yield stress by up to a factor of seven. Combined with the demonstrated potential of shear thinning artificial protein hydrogels for various uses, this reinforcement mechanism broadens the range of applications that can be addressed with shear‐thinning physical gels.     

Hybrids of Magnetic Nanoparticles with Double‐Hydrophilic Core/Shell Cylindrical Polymer Brushes and Their Alignment in a Magnetic Field

The synthesis of double‐hydrophilic core/shell cylindrical polymer brushes (CPBs), their hybrids with magnetite nanoparticles, and the directed alignment of these magnetic hybrid cylinders by a magnetic field are demonstrated. Consecutive grafting from a polyinitiator poly(2‐(2‐bromoisobutyryloxy)ethyl methacrylate) (PBIEM) of tert‐butyl methacrylate (tBMA) and oligo(ethylene glycol) methacrylate (OEGMA) using atom‐transfer radical polymerization (ATRP) and further de‐protection yields core/shell CPBs with poly(methacrylic acid) (PMAA) as the core and POEGMA as the shell, which is evidenced by ¹H NMR, gel permeation chromatography (GPC), and dynamic and static light scattering (DLS and SLS). The resulting core/shell brush is well soluble in water and shows a pH responsiveness because of its weak polyelectrolyte core. Pearl‐necklace structures are observed by cryogenic transmission electron microscopy (cryo‐TEM) at pH 4, while at pH 7, these structures disappear owing to the ionization of the core. A similar morphology is also found for the polychelate of the core/shell CPBs with Fe³⁺ ions. Superparamagnetic magnetite nanoparticles have also been prepared and introduced into the core of the brushes. The hybrid material retains the superparamagnetic property of the magnetite nanoparticles, which is verified by superconducting quantum interference device (SQUID) magnetization measurements. Large‐scale alignment of the hybrid cylinders in relatively low magnetic fields (40–300 mT) can easily be performed when deposited on a surface. which is clearly revealed by the atomic force microscopy (AFM) and TEM measurements.     

Multifunctional Nanoparticles Composed of A Poly( dl‐lactide‐coglycolide) Core and A Paramagnetic Liposome Shell for Simultaneous Magnetic Resonance Imaging and Targeted Therapeutics

A multifunctional nanoscale platform that is self‐assembled from a hydrophobic poly( dl ‐lactide‐coglycolide)(PLGA) core and a hydrophilic paramagnetic‐folate‐coated PEGylated lipid shell (PFPL; PEG=polyethylene glycol) is designed for simultaneous magnetic resonance imaging (MRI) and targeted therapeutics. The nanocomplex has a well‐defined core‐shell structure which is studied using confocal laser scanning microscopy (CLSM). The paramagnetic diethylenetriaminepentaacetic acid‐gadolinium (DTPA‐Gd) chelated to the shell layer exhibits significantly higher spin–lattice relaxivity (r₁) than the clinically used small‐molecular‐weight MRI contrast agent Magnevist^®. The PLGA core serves as a nanocontainer to load and release the hydrophobic drugs. From a drug‐release study, it is found that the modification of the PLGA core with a polymeric liposome shell can be a useful tool for reducing the drug‐release rate. Cellular uptake of folate nanocomplex is found to be higher than that of non‐folate‐nanocomplex due to the folate‐binding effect on the cell membrane. This work indicates that the multifunctional platform with combined characteristics applicable to MRI and drug delivery may have great potential in cancer chemotherapy and diagnosis.     

Electrochemically Triggered Selective Adsorption of Biotemplated Nanoparticles on Self‐Assembled Organometallic Diblock Copolymer Thin Films

The controlled adsorption of the iron‐containing cage protein ferritin at the nanoscale using stimuli‐responsive self‐assembled diblock copolymer thin‐film templates is reported. The diblock copolymer used study consists of a cylinder‐forming polystyrene‐block‐polyferrocenylsilane (PS‐b‐PFS), with PFS as the minor block, and shows reversible redox properties. To prevent any spontaneous protein adsorption on either block, the electrolyte pH is selected to leave the ferritin negatively charged, and the protein concentration and solution ionic strength are carefully tuned. Selective adsorption of ferritin on the PFS domains of the self‐assembled thin films is then triggered in situ by applying a positive potential, simultaneously oxidizing the PFS and attracting the ferritin electrostatically.     

Directed Emission from Self‐Assembled Microhelices

Bottom‐up assembly can organize simple building blocks into complex architectures for light manipulation. The optical properties of self‐assembled polycrystalline barium carbonate/silica double helices are studied using fluorescent Fourier and Mueller matrix microscopy. Helices doped with fluorescein direct light emission along the long axis of the structure. Furthermore, light transmission measured normal and parallel to the long axis exhibits twist sense‐specific circular retardance and waveguiding, respectively, although the measurements suffer from depolarization. The helices thus integrate highly directional emission with enantiomorph‐specific polarization. This optical response emerges from the arrangement of nanoscopic mineral crystallites in the microscopic helix, and demonstrates how bottom‐up assembly can achieve ordering across multiple length scales to form complex functional materials.     

Mussel Inspired Dynamic Cross‐Linking of Self‐Healing Peptide Nanofiber Network

A general drawback of supramolecular peptide networks is their weak mechanical properties. In order to overcome a similar challenge, mussels have adapted to a pH‐dependent iron complexation strategy for adhesion and curing. This strategy also provides successful stiffening and self‐healing properties. The present study is inspired by the mussel curing strategy to establish iron cross‐link points in self‐assembled peptide networks. The impact of peptide‐iron complexation on the morphology and secondary structure of the supramolecular nanofibers is characterized by scanning electron microscopy, circular dichroism and Fourier transform infrared spectroscopy. Mechanical properties of the cross‐linked network are probed by small angle oscillatory rheology and nanoindentation by atomic force microscopy. It is shown that iron complexation has no influence on self‐assembly and β‐sheet‐driven elongation of the nanofibers. On the other hand, the organic‐inorganic hybrid network of iron cross‐linked nanofibers demonstrates strong mechanical properties comparable to that of covalently cross‐linked network. Strikingly, iron cross‐linking does not inhibit intrinsic reversibility of supramolecular peptide polymers into disassembled building blocks and the self‐healing ability upon high shear load. The strategy described here could be extended to improve mechanical properties of a wide range of supramolecular polymer networks.     

Integration of Self‐Assembled Microvascular Networks with Microfabricated PEG‐Based Hydrogels

Despite tremendous efforts, tissue engineered constructs are restricted to thin, simple tissues sustained only by diffusion. The most significant barrier in tissue engineering is insufficient vascularization to deliver nutrients and metabolites during development in vitro and to facilitate rapid vascular integration in vivo. Tissue engineered constructs can be greatly improved by developing perfusable microvascular networks in vitro in order to provide transport that mimics native vascular organization and function. Here a microfluidic hydrogel is integrated with a self‐assembling pro‐vasculogenic co‐culture in a strategy to perfuse microvascular networks in vitro. This approach allows for control over microvascular network self‐assembly and employs an anastomotic interface for integration of self‐assembled microvascular networks with fabricated microchannels. As a result, transport within the system shifts from simple diffusion to vessel supported convective transport and extra‐vessel diffusion, thus improving overall mass transport properties. This work impacts the development of perfusable prevascularized tissues in vitro and ultimately tissue engineering applications in vivo.     

High‐Efficient Deep‐Blue Light‐Emitting Diodes by Using High Quality ZnxCd1‐xS/ZnS Core/Shell Quantum Dots

High‐quality violet‐blue emitting Zn_xCd_1‐xS/ZnS core/shell quantum dots (QDs) are synthesized by a new method, called “nucleation at low temperature/shell growth at high temperature”. The resulting nearly monodisperse Zn_xCd_1‐xS/ZnS core/shell QDs have high PL quantum yield (near to 100%), high color purity (FWHM) <25 nm), good color tunability in the violet‐blue optical window from 400 to 470 nm, and good chemical/photochemical stability. More importantly, the new well‐established protocols are easy to apply to large‐scale synthesis; around 37 g Zn_xCd_1‐xS/ZnS core/shell QDs can be easily synthesized in one batch reaction. Highly efficient deep‐blue quantum dot‐based light‐emitting diodes (QD‐LEDs) are demonstrated by employing the Zn_xCd_1‐xS/ZnS core/shell QDs as emitters. The bright and efficient QD‐LEDs show a maximum luminance up to 4100 cd m^?2, and peak external quantum efficiency (EQE) of 3.8%, corresponding to 1.13 cd A^?1 in luminous efficiency. Such high value of the peak EQE can be comparable with OLED technology. These results signify a remarkable progress, not only in the synthesis of high‐quality QDs but also in QD‐LEDs that offer a practicle platform for the realization of QD‐based violet‐blue display and lighting.