Combined Tumor Environment Triggered Self‐Assembling Peptide Nanofibers and Inducible Multivalent Ligand Display for Cancer Cell Targeting with Enhanced Sensitivity and Specificity

Many new technologies, such as cancer microenvironment‐induced nanoparticle targeting and multivalent ligand approach for cell surface receptors, are developed for active targeting in cancer therapy. While the principle of each technology is well illustrated, most systems suffer from low targeting specificity and sensitivity. To fill the gap, this work demonstrates a successful attempt to combine both technologies to simultaneously improve cancer cell targeting sensitivity and specificity. Specifically, the main component is a targeting ligand conjugated self‐assembling monomer precursor (SAM‐P), which, at the tumor site, undergoes tumor‐triggered cleavage to release the active form of self‐assembling monomer capable of forming supramolecular nanostructures. Biophysical characterization confirms the chemical and physical transformation of SAM‐P from unimers or oligomers with low ligand valency to supramolecular assemblies with high ligand valency under a tumor‐mimicking reductive microenvironment. The in vitro fluorescence assay shows the importance of supramolecular morphology in mediating ligand–receptor interactions and targeting sensitivity. Enhanced targeting specificity and sensitivity can be achieved via tumor‐triggered supramolecular assembly and induces multivalent ligand presentation toward cell surface receptors, respectively. The results support this combined tumor microenvironment‐induced cell targeting and multivalent ligand display approach, and have great potential for use as cell‐specific molecular imaging and therapeutic agents with high sensitivity and specificity.     

Active Self‐Assembly of Train‐Shaped DNA Nanostructures via Catalytic Hairpin Assembly Reactions

Biomolecular self‐assembly is a powerful approach for fabricating supramolecular architectures. Over the past decade, a myriad of biomolecular assemblies, such as self‐assembly proteins, lipids, and DNA nanostructures, have been used in a wide range of applications, from nano‐optics to nanoelectronics and drug delivery. The method of controlling when and where the self‐assembly starts is essential for assembly dynamics and functionalization. Here, train‐shaped DNA nanostructures are actively self‐assembled using DNA tiles as artificial “carriages,” hairpin structures as “couplers,” and initiators of catalytic hairpin assembly (CHA) reactions as “wrenches.” The initiator wrench can selectively open the hairpin couplers to couple the DNA tile carriages with high product yield. As such, DNA nanotrains are actively prepared with two, three, four, or more carriages. Furthermore, by flexibly modifying the carriages with “biotin seats” (biotin‐modified DNA tiles), streptavidin “passengers” are precisely arranged in corresponding seats. The applications of the CHA‐triggered self‐assembly mechanism are also extended for assembling the large DNA origami dimer. With the creation of 1D architectures established, it is thought that this CHA‐triggered self‐assembly mechanism may provide a new element of control for complex autonomous assemblies from a variety of starting materials with specific sites and times.     

Peptide-assisted synthesis of gold nanoparticles and their self-assembly

A novel gold nanoparticle-tripeptide (GNP-tripeptide) conjugate was prepared by peptide in-situ redox technique at ambient temperatureusing a newly designed tripeptide. This new tripeptide was nso designed that it has a C-terminus tyrosine residue, which reduced Au+3 to Au, and the terminally located free amino group was bound to the gold nanoparticle (GNP) surface resulting in highly stable Au colloids. The average diameter of the tripeptide-stabilized GNP is 8.7 +/- 2.3 nm. Tripeptide bound gold nanoparticles formed three-dimensional assemblies in the presence of an excess of similar or disimilar tripeptides. The aggregation of GNPs results in a red shift in the surface plasmon resonance from lambda max = 527 to 556 nm. The effect of the solvent, concentration, and nature of the tripeptides on the assembly process were investigated by TEM and UV-visible spectroscopy.     

A recyclable supramolecular membrane for size-selective separation of nanoparticles

Most practical materials are held together by covalent bonds, which are irreversible. Materials based on noncovalent interactions can undergo reversible self-assembly, which offers advantages in terms of fabrication, processing and recyclability, but the majority of noncovalent systems are too fragile to be competitive with covalent materials for practical applications, despite significant attempts to develop robust noncovalent arrays. Here, we report nanostructured supramolecular membranes prepared from fibrous assemblies in water. The membranes are robust due to strong hydrophobic interactions, allowing their application in the size-selective separation of both metal and semiconductor nanoparticles. A thin (12 μm) membrane is used for filtration (～5 nm cutoff), and a thicker (45 μm) membrane allows for size-selective chromatography in the sub-5 nm domain. Unlike conventional membranes, our supramolecular membranes can be disassembled using organic solvent, cleaned, reassembled and reused multiple times.     

One-pot synthesis of ZnO/Ag nanospheres with enhanced photocatalytic activity

ZnO/Ag composite nanospheres with an average diameter of about 440 nm, were synthesized through a facile one-pot solvothermal reaction, using a kind of biomolecular sodium alginate as template, H₂O and diethanolamine as solvents, followed by the assembly of ZnO and Ag nanoparticles in-situly produced. The composite spheres were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and energy disperse X-ray spectrum. Moreover, the results showed that the as-made ZnO/Ag assembled nanospheres exhibited better photocatalytic performance than the pure ZnO nanoparticles and this one-pot synthesis method has great potential to be extended for the synthesis of other metallic oxide/metal spheres.     

Properties of Dense Assemblies of Magnetic Nanoparticles Promising for Application in Biomedicine

Chemically synthesized iron oxide nanoparticles and magnetosomes produced by magnetotactic bacteria are of great importance for application in biomedicine. In this paper, we discuss the complicated magnetic anisotropy of the nanoparticles, the influence of the magnetostatic interactions, and thermal fluctuations on the behavior of these assemblies. Numerical simulation for dilute assemblies of iron oxide nanoparticles with combined magnetic anisotropy show that the uniaxial shape anisotropy dominates even for small aspect ratios of the particle, L/D≥1.1–1.2. The quasistatic hysteresis loops are calculated for various clusters of bacterial magnetosomes with diameters D=40–60 nm to understand the influence of magnetostatic interactions. The specific absorption rate (SAR) is calculated for assemblies of magnetic nanoparticles dispersed in solid and liquid media. A new electrodynamic method of measurement is used to obtain the SAR of the assembly of bacterial magnetosomes with average diameter D=48 nm.     

Construction and Functionalization of a Clathrin Assembly for a Targeted Protein Delivery (Small 8/2023)

Protein assemblies have drawn much attention as platforms for biomedical applications, including gene/drug delivery and vaccine, due to biocompatibility and functional diversity. Here, the construction and functionalization of a protein assembly composed of human clathrin heavy chain and light chain for a targeted protein delivery, is presented. The clathrin heavy and light chains are redesigned and associated with each other, and the resulting triskelion unit further self-assembled into a clathrin assembly with the size of about 28 nm in diameter. The clathrin assembly is dual-functionalized with a protein cargo and a targeting moiety using two different orthogonal protein–ligand pairs through one-pot reaction. The functionalized clathrin assembly exhibits about a 900-fold decreased K_D value for a cell-surface target due to avidity compared to a native targeting moiety. The utility of the clathrin assembly is demonstrated by an efficient delivery of a protein cargo into tumor cells in a target-specific manner, resulting in a strong cytotoxic effect. The present approach can be used in the creation of protein assemblies with multimodality.     

Tubulin Double Helix: Lateral and Longitudinal Curvature Changes of Tubulin Protofilament

By virtue of their native structures, tubulin dimers are protein building blocks that are naturally preprogrammed to assemble into microtubules (MTs), which are cytoskeletal polymers. Here, polycation‐directed (i.e., electrostatically tunable) assembly of tubulins is demonstrated by conformational changes to the tubulin protofilament in longitudinal and lateral directions, creating tubulin double helices and various tubular architectures. Synchrotron small‐angle X‐ray scattering and transmission electron microscopy reveal a remarkable range of nanoscale assembly structures: single‐ and double‐layered double‐helix tubulin tubules. The phase transitions from MTs to the new assemblies are dependent on the size and concentration of polycations. Two characteristic scales that determine the number of observed phases are the size of polycation compared to the size of tubulin (≈4 nm) and to MT diameter (≈25 nm). This work suggests the feasibility of using polycations that have scissor‐ and glue‐like properties to achieve “programmable breakdown” of protein nanotubes, tearing MTs into double‐stranded tubulins and building up previously undiscovered nanostructures. Importantly, a new role of tubulins is defined as 2D shape‐controllable building blocks for supramolecular architectures. These findings provide insight into the design of protein‐based functional materials, for example, as metallization templates for nanoscale electronic devices, molecular screws, and drug delivery vehicles.     

Conductive polymer preparation under extreme or non-classical conditions

Polyaniline (PANI) emeraldine salt form and PANI/silver composites have been synthesized by sonochemical and ionizing radiation methods. These composite materials were obtained through sonication and γ irradiation of an aqueous solution of aniline and silver nitrate, in room temperature, respectively. The mechanisms suggested to explain the formation of these products are based on the fact that both methods produce hydroxyl radical ^•OH and hydrogen radical ^•H, where hydroxyl radical ^•OH acts as an oxidizing agent in the polymerization process of aniline monomer; and hydrogen radical ^•H, as a reducing agent for silver ions. Spectroscopic, X-ray, and SEM measures show that PANI and silver nano particles of 40 nm average diameter are produced with ultrasonic methods, whereas silver nano particles of 60 nm average, and fibrillar, highly network morphology for PANI with 60 nm fibrillar diameter average are obtained using γ radiation).     

Large‐Area 3D Hierarchical Superstructures Assembled from Colloidal Nanoparticles

Assembling nanosized building blocks into macroscopic 3D complex structures is challenging. Here, nanosized metal and semiconductor building blocks with a variety of sizes and shapes (spheres, stars, and rods) are successfully assembled into a broad range of hierarchical (nanometer to micrometer) assemblies of functional materials in centimeter size using butterfly wings as templates. This is achieved by the introduction of steric hindrance to the assembly process, which compensates for attraction from the environmentally sensitive hydrogen bonds and prevents the aggregation of nanosized building blocks. Of these materials, Au nanostar assemblies show a superior enhancement in surface‐enhanced Raman scattering (SERS) performance (rhodamine 6G, 1506 cm^?1) under 532, 633, and 780 nm excitation—this is 3.1–4.4, 3.6–3.9, and 2.9–47.3 folds surpassing Au nanosphere assemblies and commercial SERS substrates (Q‐SERS), respectively. This method provides a versatile route for the assembly of various nanosized building blocks into different 3D superstructures and for the construction of hybrid nanomaterials and nanocomposites.     

具有三维网状结构的石墨相氮化碳/还原氧化石墨烯/钯复合材料的合成及可见光催化性能

石墨相氮化碳(g-C_3N_4)已经被认为是一种高效的非金属半导体光催化剂。为进一步优化其光催化性能,通过热解-水热两步法制备了三维网状结构的g-C_3N_4/还原氧化石墨烯(rGO)/钯纳米颗粒(Pd NPs)复合材料。该复合材料由大量超薄片组成,而且薄片上有大量直径约为10nm的Pd NPs。g-C_3N_4/rGO/Pd NPs复合材料展现了一个宽的可见光吸收(边~460nm),其在460~800nm波长范围内还有一个随波长增加的光吸收。经可见光(λ400nm)照射140 min后,g-C_3N_4/rGO/Pd NPs复合材料可降解90%罗丹明B(RhB)。此外,循环实验表明g-C_3N_4/rGO/Pd NPs复合材料具有良好的稳定性。因此,g-C_3N_4/rGO/Pd NPs复合材料有望成为一种高效稳定的光催化剂,在水污染处理领域具有潜在的应用价值。     

Assembling of dense fluorescent supramolecular webs via self-propelled star-shaped aggregates

We report a novel mechanism of assembly of dendronized rod molecules into a dense supramolecular fluorescencent web featuring self-propelled mechanistic inward motion of star-shaped aggregates within a solution droplet. We suggest that such a motion (observed in real time) is caused by the self-repulsion of the growing star-shaped nuclei from the liquid-solid-air interface in the course of one-dimensional growth of the anchored arms. An intriguing mechanism discovered here involves microscopic (hundred micrometers) directional motion of the microscopic aggregates driven by one-dimensional molecular assembly, which opens a new venue for guided assembly of dense mesoscopic supramolecular webs. Such assemblies can serve as interesting microfluidic networks, a web of optical switches, and model systems for studying intercellular communication.     

Template‐Free Growth of Well‐Ordered Silver Nano Forest/Ceramic Metamaterial Films with Tunable Optical Responses

Currently, the limitations of conventional methods for fabricating metamaterials composed of well‐aligned nanoscale inclusions either lack the necessary freedom to tune the structural geometry or are difficult for large‐area synthesis. In this Communication, the authors propose a fabrication route to create well‐ordered silver nano forest/ceramic composite single‐layer or multi‐layer vertically stacked structures, as a distinctive approach to make large‐area nanoscale metamaterials. To take advantage of direct growth, the authors fabricate single‐layer nanocomposite films with a well‐defined sub‐5 nm interwire gap and an average nanowire diameter of ≈3 nm. Further, artificially constructed multilayer metamaterial films are easily fabricated by vertical integration of different single‐layer metamaterial films. Based upon the thermodynamics as well as thin film growth dynamics theory, the growth mechanism is presented to elucidate the formation of such structure. Intriguing steady and transient optical properties in these assemblies are demonstrated, owing to their nanoscale structural anisotropy. The studies suggest that the self‐organized nanocomposites provide an extensible material platform to manipulate optical response in the region of sub‐5 nm scale.     

Tuning the Amphiphilicity of Building Blocks: Controlled Self‐Assembly and Disassembly for Functional Supramolecular Materials

Amphiphilicity is one of the molecular bases for self‐assembly. By tuning the amphiphilicity of building blocks, controllable self‐assembly can be realized. This article reviews different routes for tuning amphiphilicity and discusses different possibilities for self‐assembly and disassembly in a controlled manner. In general, this includes irreversible and reversible routes. The irreversible routes concern irreversible reactions taking place on the building blocks and changing their molecular amphiphilicity. The building blocks are then able to self‐assemble to form different supramolecular structures, but cannot remain stable upon loss of amphiphilicity. Compared to the irreversible routes, the reversible routes are more attractive due to the good control over the assembly and disassembly of the supramolecular structure formed via tuning of the amphiphilicity. These routes involve reversible chemical reactions and supramolecular approaches, and different external stimuli can be used to trigger reversible changes of amphiphilicity, including light, redox, pH, and enzymes. It is anticipated that this line of research can lead to the fabrication of new functional supramolecular assemblies and materials.     

Metal Ion‐Induced Self‐Assembly of a Multi‐Responsive Block Copolypeptide into Well‐Defined Nanocapsules

Protein cages are an interesting class of biomaterials with potential applications in bionanotechnology. Therefore, substantial effort is spent on the development of capsule‐forming designer polypeptides with a tailor‐made assembly profile. The expanded assembly profile of a triblock copolypeptide consisting of a metal ion chelating hexahistidine‐tag, a stimulus‐responsive elastin‐like polypeptide block, and a pH‐responsive morphology‐controlling viral capsid protein is presented. The self‐assembly of this multi‐responsive protein‐based block copolymer is triggered by the addition of divalent metal ions. This assembly process yields monodisperse nanocapsules with a 20 nm diameter composed of 60 polypeptides. The well‐defined nanoparticles are the result of the emergent properties of all the blocks of the polypeptide. These results demonstrate the feasibility of hexahistidine‐tags to function as supramolecular cross‐linkers. Furthermore, their potential for the metal ion‐mediated encapsulation of hexahistidine‐tagged proteins is shown.     

Metal assisted self-assembled nano sized porous 2-D structures incorporating malonic acid dihydrazide and melamine

The solids Cu(MADH)₂·Cl₂·2TAT·9H₂O and Zn(MADH)₂·Cl₂·2TAT·2H₂O (MADH = malonic acid dihydrazide and TAT = melamine) characterized by spectroscopic and elemental analysis, have been investigated by transmission electron microscope. Microstructure at high magnification revealed the supramolecular assembly of MADH and TAT into a mesh structure in presence of Cu(II) metal ions and tubular structure with intermittent openings on the tube walls and Y- junctions for Zn(II) complex. The mesh structure of the Cu(II) complex has uniformly spaced 40–50 nm long and 20–30 nm wide openings, while the diameter of the tubular structure of the Zn(II) complex is 50–200 nm.The assembly of the supramolecular structure is attributed to H-bonding and the different architectures of the assembly with different metal ions to the difference in waters of crystallization. The potential of the complex for gas adsorption was also investigated.     

A size controlled synthesis of CuS nano-particles in the protein cage,apoferritin

CuS compound semiconductor nanoparticles (NPs) were prepared in the 7 nm inner cavity of apoferritin, a cage-shaped protein composed of 24 subunits forming a cage-like structure, 12 nm in diameter. The average core diameter of the NPs synthesized in the apoferritin cavity was 5 nm with narrow size distribution. The synthesized NP cores were analyzed and confirmed by EDS, XRD and HR-TEM as hexagonal poly crystalline. The CuS NP core synthesis took 3 h and the synthesis manner was all-or-nothing core formation. This water-soluble and homogeneous CuS semiconductor NP has the potential to be used in the construction of nanostructures.     

Two‐Step Assembly of Thermoresponsive Gold Nanorods Coated with a Single Kind of Ligand

Gold nanorods (GNRs) coated with a single kind of ligand show thermoreponsive two‐step assembly to provide a hierarchical structure. The GNRs (33 nm in length × 14 nm in diameter) coated with a hexa(ethylene glycol) (HEG) derivative form side‐by‐side assemblies at 30 °C (T_A1) as a steady state through dehydration. By further heating to over 40 °C (T_A2), larger assemblies, which are composed of the side‐by‐side assembled units, are formed as hierarchical structures. The dehydration temperature of the HEG derivative varies depending on the free volume of the HEG unit, which corresponds to the curvature of the GNRs. Upon heating, dehydration first occurs from the ligands on the side portions with a lower curvature, and then from the ligands on the edge portions with a higher curvature. The different sized GNRs (33 × 8 and 54 × 15 nm) also show two‐step assembly. Both the T_A1 and T_A2 are dependent on the diameter of the GNRs, but independent of their length. This result supports that the dehydration is dependent on the free volume, which corresponds to the curvature. Anisotropic assembly focusing on differences in curvature provides new guidelines for the fabrication of hierarchical structures.     

Synthesis and photo-degradation application of WO3/TiO2 hollow spheres

A WO(3)/TiO(2) composite, hollow-sphere photocatalyst with average diameter of 320 nm and shell thickness of 50 nm was successfully prepared using a template method. UV-vis diffuse reflectance spectra illustrated that the main absorption edges of the WO(3)/TiO(2) hollow spheres were red-shifted compared to the TiO(2) hollow spheres, indicating an extension of light absorption into the visible region of the composite photocatalyst. The WO(3) and TiO(2) phases were confirmed by X-ray diffraction analysis. BET isotherms revealed that the specific surface area and average pore diameter of the hollow spheres were 40.95 m(2)/g and 19 nm, respectively. Photocatalytic experiments indicate that 78% MB was degraded by WO(3)/TiO(2) hollow spheres under visible light within 80 min. Under the same conditions, only 24% MB can be photodegraded by TiO(2). The photocatalytic mineralization of MB, catalyzed by TiO(2) and WO(3)/TiO(2), proceeded at a significantly higher rate under UV irradiation than that under visible light, and more significant was the increase in the apparent rate constant with the WO(3)/TiO(2) composite semiconductor material which was 3.2- and 3.5-fold higher than with the TiO(2) material under both UV and visible light irradiation. The increased photocatalytic activity of the coupled nanocomposites was attributed to photoelectron/hole separation efficiency and the extension of the wavelength range of photoexcitation.     

Patterning of Lyotropic Chromonic Liquid Crystals by Photoalignment with Photonic Metamasks

Controlling supramolecular self‐assembly in water‐based solutions is an important problem of interdisciplinary character that impacts the development of many functional materials and systems. Significant progress in aqueous self‐assembly and templating has been demonstrated by using lyotropic chromonic liquid crystals (LCLCs) as these materials show spontaneous orientational order caused by unidirectional stacking of plank‐like molecules into elongated aggregates. In this work, it is demonstrated that the alignment direction of chromonic assemblies can be patterned into complex spatially‐varying structures with very high micrometer‐scale precision. The approach uses photoalignment with light beams that exhibit a spatially‐varying direction of light polarization. The state of polarization is imprinted into a layer of photosensitive dye that is protected against dissolution into the LCLC by a liquid crystalline polymer layer. The demonstrated level of control over the spatial orientation of LCLC opens opportunities for engineering materials and devices for optical and biological applications.