Frame‐Guided Assembly of Vesicles with Programmed Geometry and Dimensions

In molecular self‐assembly molecules form organized structures or patterns. The control of the self‐assembly process is an important and challenging topic. Inspired by the cytoskeletal‐membrane protein lipid bilayer system that determines the shape of eukaryotic cells, we developed a frame‐guided assembly process as a general strategy to prepare heterovesicles with programmed geometry and dimensions. This method offers greater control over self‐assembly which may benefit the understanding of the formation mechanism as well as the functions of the cell membrane.     

Thermally Triggered Frame‐Guided Assembly

We report a thermally triggered frame‐guided assembly (FGA) strategy for the preparation of vesicles. We employ thermally responsive poly(propylene oxide) (PPO) to make the leading hydrophobic groups (LHGs) thermally responsive, so that they are hydrophilic below the low critical solution temperature (LCST) and the frame forms in a homogeneous environment. When the temperature is increased above the LCST, the LHGs become hydrophobic and the assembly process is triggered, which drives DNA‐b‐PPO to assemble around the LHGs, forming vesicles. This work verified that FGA is a general strategy and can be applied to polymeric systems. The thermally triggered assembly not only provides more controllability over the FGA process but also promotes an in‐depth understanding of the FGA strategy and in a broad view, the formation mechanism and functions of cell membrane.     

Flow‐Guided Assembly Processes

This Concept article focuses on capillary, hydrodynamics and electrokinetic flow‐guided assembly processes that can produce patterned or gradient functional surfaces either on solid surfaces or in deep micro‐ and nanoscale channels. This concept has the potential to produce low‐cost nanostructures, internal surface modifications, and devices in nanomedicine.     

Self‐Assembly Structure Formation during the Digestion of Human Breast Milk

An infant′s complete diet, human breast milk, is the basis for its survival and development. It contains water‐soluble and poorly water‐soluble bioactive components, metabolic messages, and energy, all of which are made bioavailable during the digestion process in the infant′s gastrointestinal tract. Reported is the first discovery of highly geometrically organized structures formed during the digestion of human breast milk under simulated in vivo conditions using small‐angle X‐ray scattering and cryogenic transmission electron microscopy. Time of digestion, pH, and bile salt concentration were found to have symbiotic effects gradually tuning the oil‐based environment inside the breast milk globules to more water‐like structures with high internal surface area. The structure formation is necessarily linked to its function as carriers for poorly water‐soluble molecules in the digestive tract of the infant.     

Controllable Self‐Assembly of Organic–Inorganic Amphiphiles Containing Dawson Polyoxometalate Clusters

An organic–inorganic molecular hybrid containing the Dawson polyoxometalate, ((C₄H₉)₄N)₅H‐ [P₂V₃W₁₅O₅₉(OCH₂)₃CNHCOC₁₅H₃₁], was synthesized and its surfactant‐like amphiphilic properties, represented by the formation of bilayer vesicles, were studied in polar solvents. The vesicle size decreases with both decreasing hybrid concentration and with increasing polarity of the solvent, independently. The self‐assembly behavior of this hybrid can be controlled by introducing different counterions into the acetonitrile solutions. The addition of ZnCl₂ and NaI can cause a gradual decrease and increase of vesicular sizes, respectively. Tetraalkylammonium bromide is found to disassemble the vesicle assemblies. Moreover, the original counterions of the hybrid can be replaced with protons, resulting in pH‐dependent formation of vesicles in aqueous solutions. The hybrid surfactant can further form micro‐needle structures in aqueous solutions upon addition of Ca²⁺ ions.     

Synthesis of Aromatic Macrocyclic Amphiphiles and their Self‐Assembling Behavior in Aqueous Solution

A triblock amphiphilic macrocycle consisting of a macrocyclic aromatic segment, a hydrophilic oligo(ethylene oxide) branch, and a hydrophobic alkyl dendron is successfully synthesized and characterized. The resulting cyclic amphiphile is observed to self‐assemble into hollow double‐layered capsules in aqueous solution, as confirmed by dynamic light scattering and cryogenic transmission electron microscopy investigations. The capsules are able to encapsulate hydrophobic guest molecules through aromatic interactions with high stability.

     

Access to Different Nanostructures via Self‐Assembly of Thiourea‐Containing PEGylated Amphiphiles

Readily water‐soluble PEGylated amphiphiles containing bis‐thiourea‐based molecular recognition units at the interface of hydrophobic and hydrophilic blocks are developed. Self‐assembly of these amphiphiles is found to be dependent on the exact chemical composition of the hydrophobic component. Elongated, spherical, and disk‐like micelles are formed with the change in hydrophobic group from stearyl (2A), oleyl (2B), and dodecanol (2C), respectively. The length of the rod‐like elongated micelles formed by 2A could be tuned by thermal treatment as well. Synthesis and detailed structural characterization of these amphiphiles by TEM, DSC, synchrotron SAXS techniques are reported. Organic solvent‐free direct aqueous encapsulation of doxorubicin, an anticancer drug into these nanostructures is demonstrated.

     

Construction of Liposomes Mimicking Cell Membrane Structure through Frame‐Guided Assembly

The shape of eukaryotic cells is determined by the cytoskeleton associated with membrane proteins; however, the detailed mechanism of how the integral morphologies with structural stability is generated and maintained is still not fully understood. Here, based on the Frame‐Guided Assembly (FGA) strategy, we successfully prepared hetero‐liposomes with structural composition similar to that of eukaryotic cells by screening a series of transmembrane peptides as the leading hydrophobic groups (LHGs). It was demonstrated that the conformation and transmembrane mode of the LHGs played dominant roles during the FGA process. The FGA liposomes were formed with excellent stability, which may further provide evidence for the cytoskeleton–membrane protein–lipid bilayer model. Taking advantage of the biocompatibility and stability, the FGA liposomes were also applied to prepare novel drug delivery vehicles, which is promising in diagnostic imaging and cancer therapy applications.     

Nonionic Dendritic and Carbohydrate Based Amphiphiles: Self‐Assembly and Transport Behavior

Herein, a new series of non‐ionic dendritic and carbohydrate based amphiphiles is synthesized employing biocompatible starting materials and studied for supramolecular aggregate formation in aqueous solution. The dendritic amphiphiles 12 and 13 possessing poly(glycerol) [G2.0] as hydrophilic unit and C‐10 and C‐18 hydrophobic alkyl chains, respectively, exhibit low critical aggregation concentration (CAC) in the order of 10⁻⁵m and hydrodynamic diameters in the 8–10 nm range and supplemented by cryogenic transmission electron microscopy. Ultraviolet‐visible (UV‐Vis) and fluorescence spectroscopy suggests the effective solubilization of hydrophobic guests by the self‐assembled architectures, with the nanotransporters 12 and 13 possessing the highest encapsulation efficiency of 80.74 and 98.03% for curcumin. Efficient uptake of encapsulated curcumin in adenocarcinomic human alveolar basal epithelial (A549) cells is observed by confocal laser scanning microscopy. Amphiphiles 12 and 13 are non‐cytotoxic at the concentrations studied, however, curcumin encapsulated samples efficiently reduce the viability of A549 cells in vitro. Experimental studies indicate the ability of amphiphile 13 to encapsulate 1‐anilinonaphthalene‐8‐sulfonic acid (ANS) and curcumin with binding constant of 1.16 × 105⁵m ⁻¹ and 1.43 × 10⁶m ⁻¹, respectively. Overall, our findings demonstrate the potential of these dendritic amphiphiles for the development of prospective nanocarriers for the solubilization of hydrophobic drugs.     

All‐Conjugated,Rod‐Rod Block Copolymers‐Generation and Self‐Assembly Properties

Based on their rigid‐rod structure all‐conjugated, rod‐rod block copolymers show a preferred tendency to self‐assemble into low‐curvature vesicular or lamellar nanostructures independent from their specific chemical structure and composition. This unique and attractive behaviour is clearly illustrated in a few examples of such all‐conjugated block copolymers. The resulting nanostructured heteromaterials may find applications in electronic devices or artificial membranes.

     

Self‐Assembly of Amphiphilic Block Copolymer‐Tethered Nanoparticles: a New Approach to Nanoscale Design of Functional Materials

Colloidal molecules constructed from polymers and nanoparticles (NPs) have recently emerged as a novel class of building blocks for assembling functional hybrid materials. Particularly, self‐assembly of amphiphilic block copolymer (BCP)‐tethered NPs (BNPs) has shown great promise in the nanoscale design of functional hybrid materials. On the one hand, structurally the BNPs can be considered as molecular equivalents that are capable of self‐assembly at multiple hierarchical levels. On the other hand, the assembly of BNPs shows significant differences from molecular assembly due to their large dimension, complex geometry, and multi‐scale interactions involved in the assembly process. The manipulation of BCPs localized near the surface of the NPs offers an effective tool for engineering the interactions between NPs and hence the complexity of NP assembly. In this Feature Article, recent progresses on the self‐assembly of BNPs into functional materials are summarized. First, major strategies for assembling amphiphilic BNPs are highlighted. Secondly, the application of hybrid nanostructures (e.g., vesicles) assembled from BNPs in the field of biomedical imaging and delivery is discussed. Finally, current challenges and perspectives at this frontier are outlined.

     

Hydrogen‐Bond‐Guided Self‐Assembly of Nucleotides on a Receptor‐Array Surface

The hydrogen‐bond‐guided self‐assembly of 5′‐ribonucleotides bearing adenine(A), cytosine (C), uracil (U), or guanine (G) bases from aqueous solution on a lipid‐like surface decorated with synthetic bis(Zn^II–cyclen) (cyclen=1,4,7,10‐tetraazacyclodododecane) metal–complex receptor sites is described. The process was studied by using surface plasmon resonance spectroscopy. The data show that the mechanism of nucleotide binding to the 2D template is influenced by the chemistry of the bases and the pH value of the solution. In a neutral solution of pH 7.5, the process is cooperative and selective with respect to Watson–Crick pairs (A–U and C–G), which form stable double planes in accordance with the Chargaff rule. In a more acidic solution at pH 6.0, the interactions between complementary partners become non‐cooperative and the surface also stabilizes mismatched and wobble pairs due to the pH‐induced changes in the receptor coordination state. The results suggest that hydrogen bonding plays a key role in the self‐assembly of complementary nucleotides at the lipid‐like interface, and the cooperative character of the process stems from the ideal matching of the orientation and chemistry of all the interacting components with respect to each other in neutral solution.     

Self‐Assembly of Fullerene‐Based Janus Particles in Solution: Effects of Molecular Architecture and Solvent

Two molecular Janus particles based on amphiphilic [60]fullerene (C₆₀) derivatives were designed and synthesized by using the regioselective Bingel–Hirsh reaction and the click reaction. These particles contain carboxylic acid functional groups, a hydrophilic fullerene (AC₆₀), and a hydrophobic C₆₀ in different ratios and have distinct molecular architectures: 1:1 (AC₆₀–C₆₀) and 1:2 (AC₆₀–2C₆₀). These molecular Janus particles can self‐assemble in solution to form aggregates with various types of micellar morphology. Whereas vesicular morphology was observed for both AC₆₀–C₆₀ and AC₆₀–2C₆₀ in tetrahydrofuran, in a mixture of N,N‐dimethylformamide (DMF)/water, spherical micelles and cylindrical micelles were observed for AC₆₀–C₆₀ and AC₆₀–2C₆₀, respectively. A mechanism of formation was tentatively proposed based on the effects of molecular architecture and solvent polarity on self‐assembly.     

Aqueous Self‐Assembly of Purely Hydrophilic Block Copolymers into Giant Vesicles

Self‐assembly of macromolecules is fundamental to life itself, and historically, these systems have been primitively mimicked by the development of amphiphilic systems, driven by the hydrophobic effect. Herein, we demonstrate that self‐assembly of purely hydrophilic systems can be readily achieved with similar ease and success. We have synthesized double hydrophilic block copolymers from polysaccharides and poly(ethylene oxide) or poly(sarcosine) to yield high molar mass diblock copolymers through oxime chemistry. These hydrophilic materials can easily assemble into nanosized (<500 nm) and microsized (>5 μm) polymeric vesicles depending on concentration and diblock composition. Because of the solely hydrophilic nature of these materials, we expect them to be extraordinarily water permeable systems that would be well suited for use as cellular mimics.     

Dendronized Triangular Oligo(phenylene ethynylene) Amphiphiles: Nanofibrillar Self‐Assembly and Dye Encapsulation

Triangular‐shaped oligo(phenylene ethynylene) amphiphiles 1 a and 1 b decorated in their periphery with two‐ and four‐branched hydrophilic triethyleneglycol dendron wedges, have been synthesized and their self‐assembling properties in solution and onto surfaces investigated. The steric demand produced by the dendritic substituents induces a face‐to‐face rotated π stacking of the aromatic moieties. Studies on the concentration and temperature dependence confirm this mechanism and provide binding constants of 1.2×10⁵ and 1.7×10⁵ M ^?1 in acetonitrile for 1 a and 1 b , respectively. Dynamic and static light scattering measurements complement the study of the self‐assembly in solution and demonstrate the formation of rod‐like supramolecular structures in aqueous solution. The nanofibers formed in solution can be efficiently transferred onto surfaces. Thus, TEM images reveal the presence of strands of various thickness, with the most common being several micrometers long and with diameters of around 70 nm. Some of these nanofibers present folded edges that are indicative of their ribbon‐like nature. Interestingly, compound 1 b can also form thick filaments with a rope‐like appearance, which points to a chiral arrangement of the fibers. AFM images under highly diluted conditions also reveal long fibers with height profiles that fit well with the molecular dimensions calculated for both amphiphiles. Finally, we have demonstrated the intercalation of the hydrophobic dye Disperse Orange 3 within the filaments and its subsequent release upon increasing the temperature.     

Hydrophobic Self‐Assembly Affords Robust Noncovalent Polymer Isomers

In covalent polymerization, a single monomer can result in different polymer structures due to positional, geometric, or stereoisomerism. We demonstrate that strong hydrophobic interactions result in stable noncovalent polymer isomers that are based on the same covalent unit (amphiphilic perylene diimide). These isomers have different structures and electronic/photonic properties, and are stable in water, even upon prolonged heating at 100 °C. Such combination of covalent‐like stability together with structural/functional variation is unique for noncovalent polymers, substantially advancing their potential as functional materials.