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.     

Mastering Dendrimer Self‐Assembly for Efficient siRNA Delivery: From Conceptual Design to In Vivo Efficient Gene Silencing

Self‐assembly is a fundamental concept and a powerful approach in molecular science. However, creating functional materials with the desired properties through self‐assembly remains challenging. In this work, through a combination of experimental and computational approaches, the self‐assembly of small amphiphilic dendrons into nanosized supramolecular dendrimer micelles with a degree of structural definition similar to traditional covalent high‐generation dendrimers is reported. It is demonstrated that, with the optimal balance of hydrophobicity and hydrophilicity, one of the self‐assembled nanomicellar systems, totally devoid of toxic side effects, is able to deliver small interfering RNA and achieve effective gene silencing both in cells – including the highly refractory human hematopoietic CD34⁺ stem cells – and in vivo, thus paving the way for future biomedical implementation. This work presents a case study of the concept of generating functional supramolecular dendrimers via self‐assembly. The ability of carefully designed and gauged building blocks to assemble into supramolecular structures opens new perspectives on the design of self‐assembling nanosystems for complex and functional applications.     

Supramolecular Materials via Block Copolymer Self‐Assembly

This review discusses the potential of block copolymer type macromolecular building blocks for the preparation of self‐assembled materials. Three different classes of block copolymer type architectures will be distinguished: (i) coil–coil diblock copolymers, (ii) rod–coil diblock copolymers, and (iii) rod–coil diblock oligomers. The basic principles that underlie the self‐assembly of each of these different building blocks will be discussed. These theoretical considerations are complemented with examples from recent literature that illustrate the potential of the different types of block copolymers to prepare (functional) supramolecular materials. Finally, several strategies will be presented that could allow the preparation of stimuli‐sensitive self‐assembled materials, i.e., materials whose properties can be reversibly manipulated under the action of appropriate external stimuli.     

Multifunctional Nanoparticles Self‐Assembled from Small Organic Building Blocks for Biomedicine

Supramolecular self‐assembly shows significant potential to construct responsive materials. By tailoring the structural parameters of organic building blocks, nanosystems can be fabricated, whose performance in catalysis, energy storage and conversion, and biomedicine has been explored. Since small organic building blocks are structurally simple, easily modified, and reproducible, they are frequently employed in supramolecular self‐assembly and materials science. The dynamic and adaptive nature of self‐assembled nanoarchitectures affords an enhanced sensitivity to the changes in environmental conditions, favoring their applications in controllable drug release and bioimaging. Here, recent significant research advancements of small‐organic‐molecule self‐assembled nanoarchitectures toward biomedical applications are highlighted. Functionalized assemblies, mainly including vesicles, nanoparticles, and micelles are categorized according to their topological morphologies and functions. These nanoarchitectures with different topologies possess distinguishing advantages in biological applications, well incarnating the structure–property relationship. By presenting some important discoveries, three domains of these nanoarchitectures in biomedical research are covered, including biosensors, bioimaging, and controlled release/therapy. The strategies regarding how to design and characterize organic assemblies to exhibit biomedical applications are also discussed. Up‐to‐date research developments in the field are provided and research challenges to be overcome in future studies are revealed.     

Programmable Construction of Peptide‐Based Materials in Living Subjects: From Modular Design and Morphological Control to Theranostics

Self‐assembled nanomaterials show potential high efficiency as theranostics for high‐performance bioimaging and disease treatment. However, the superstructures of pre‐assembled nanomaterials may change in the complicated physiological conditions, resulting in compromised properties and/or biofunctions. Taking advantage of chemical self‐assembly and biomedicine, a new strategy of “in vivo self‐assembly” is proposed to in situ construct functional nanomaterials in living subjects to explore new biological effects. Herein, recent advances on peptide‐based nanomaterials constructed by the in vivo self‐assembly strategy are summarized. Modular peptide building blocks with various functions, such as targeting, self‐assembly, tailoring, and biofunctional motifs, are employed for the construction of nanomaterials. Then, self‐assembly of these building blocks in living systems to construct various morphologies of nanostructures and corresponding unique biological effects, such as assembly/aggregation‐induced retention (AIR), are introduced, followed by their applications in high‐performance drug delivery and bioimaging. Finally, an outlook and perspective toward future developments of in vivo self‐assembled peptide‐based nanomaterials for translational medicine are concluded.     

Interface‐Directed Self‐Assembly of Cell‐Laden Microgels

Cell‐laden hydrogels show great promise for creating engineered tissues. However, a major shortcoming with these systems has been the inability to fabricate structures with controlled micrometer‐scale features on a biologically relevant length scale. In this Full Paper, a rapid method is demonstrated for creating centimeter‐scale, cell‐laden hydrogels through the assembly of shape‐controlled microgels or a liquid–air interface. Cell‐laden microgels of specific shapes are randomly placed on the surface of a high‐density, hydrophobic solution, induced to aggregate and then crosslinked into macroscale tissue‐like structures. The resulting assemblies are cell‐laden hydrogel sheets consisting of tightly packed, ordered microgel units. In addition, a hierarchical approach creates complex multigel building blocks, which are then assembled into tissues with precise spatial control over the cell distribution. The results demonstrate that forces at an air–liquid interface can be used to self‐assemble spatially controllable, cocultured tissue‐like structures.     

Reversible Anion‐Driven Switching of an Organic 2D Crystal at a Solid–Liquid Interface

Ionic self‐assembly of charged molecular building blocks relies on the interplay between long‐range electrostatic forces and short‐range, often cooperative, supramolecular interactions, yet has been seldom studied in two dimensions at the solid–liquid interface. Here, we demonstrate anion‐driven switching of two‐dimensional (2D) crystal structure at the Au(111)/octanoic acid interface. Using scanning tunneling microscopy (STM), three organic salts with identical polyaromatic cation (PQPC₆⁺) but different anions (perchlorate, anthraquinonedisulfonate, benzenesulfonate) are shown to form distinct, highly ordered self‐assembled structures. Reversible switching of the supramolecular arrangement is demonstrated by in situ exchange of the anion on the pre‐formed adlayer, by changing the concentration ratio between the incoming and outgoing anion. Density functional theory (DFT) calculations reveal that perchlorate is highly mobile in the adlayer, and corroborate why this anion is only resolved transiently in STM. Surprisingly, the templating effect of the anion persists even where it does not become part of the adlayer 2D fabric, which we ascribe to differences in stabilization of cation conformations by the anion. Our results provide important insight into the structuring of mixed anion–cation adlayers. This is essential in the design of tectons for ionic self‐assembled superstructures and biomimetic adaptive materials and valuable also to understand adsorbate–adsorbate interactions in heterogeneous catalysis.     

Supramolecular Polymers: Rigid Dimers Formed through Strong Interdigitated H‐Bonds Yield Compact 1D Supramolecular Helical Polymers (Small 3/2011)

Hierarchical self‐assembly of small abiotic molecular modules interacting through noncovalent forces is increasingly being used to generate functional structures and materials for electronic, catalytic, and biomedical applications. The greatest control over the geometry in H‐bond supramolecular architectures, especially in H‐bonded supramolecular polymers, can be achieved by using conformationally rigid molecular modules undergoing self‐assembly through strong H‐bonds. Their binding strength depends on the multiplicity of the H‐bonds, the nature of donor/acceptor pairs and their secondary attractive/repulsive interactions. Here a functionalized molecular module is described, which is capable of self‐associating through self‐complementary H‐bonding patterns comprising four strong and two medium‐strength H‐bonds to form dimers. The self‐association of these phenylpyrimidine‐based dimers through directional H‐bonding between two lateral pyridin‐2(1H)‐one units of neighboring molecules allows the formation of highly compact 1D supramolecular polymers by self‐assembly on graphite. A concentration‐dependent study by scanning tunneling microscopy at the solid–liquid interface, corroborated by dispersion‐corrected density functional studies, reveals the controlled generation of either linear supramolecular 2D arrays, or long helical supramolecular polymers with a high shape persistence.     

Supramolecular Crystal Engineering at the Solid–Liquid Interface from First Principles: Toward Unraveling the Thermodynamics of 2D Self‐Assembly

The formation of highly ordered 2D supramolecular architectures self‐assembled at the solid–solution interfaces is subject to complex interactions between the analytes, the solvent, and the substrate. These forces have to be mastered in order to regard self‐assembly as an effective bottom‐up approach for functional‐device engineering. At such interfaces, prediction of the thermodynamics governing the formation of spatially ordered 2D arrangements is far from being fully understood, even for the physisorption of a single molecular component on the basal plane of a flat surface. Two recent contributions on controlled polymorphism and nanopattern formation render it possible to gain semi‐quantitative insight into the thermodynamics of physisorption at interfaces, paving the way towards 2D supramolecular crystal engineering. Although in these two works different systems have been chosen to tackle such a complex task, authors showed that the chemical design of molecular building blocks is not the only requirement to fulfill when trying to preprogram self‐assembled patterns at the solid–liquid interface.     

Assembly and Self‐Assembly of Nanomembrane Materials—From 2D to 3D

Nanoscience and nanotechnology offer great opportunities and challenges in both fundamental research and practical applications, which require precise control of building blocks with micro/nanoscale resolution in both individual and mass‐production ways. The recent and intensive nanotechnology development gives birth to a new focus on nanomembrane materials, which are defined as structures with thickness limited to about one to several hundred nanometers and with much larger (typically at least two orders of magnitude larger, or even macroscopic scale) lateral dimensions. Nanomembranes can be readily processed in an accurate manner and integrated into functional devices and systems. In this Review, a nanotechnology perspective of nanomembranes is provided, with examples of science and applications in semiconductor, metal, insulator, polymer, and composite materials. Assisted assembly of nanomembranes leads to wrinkled/buckled geometries for flexible electronics and stacked structures for applications in photonics and thermoelectrics. Inspired by kirigami/origami, self‐assembled 3D structures are constructed via strain engineering. Many advanced materials have begun to be explored in the format of nanomembranes and extend to biomimetic and 2D materials for various applications. Nanomembranes, as a new type of nanomaterials, allow nanotechnology in a controllable and precise way for practical applications and promise great potential for future nanorelated products.     

Self‐Assembly of Shaped Nanoparticles into Free‐Standing 2D and 3D Superlattices

This article describes a novel supramolecular assembly‐mediated strategy for the organization of Au nanoparticles (NPs) with different shapes (e.g., spheres, rods, and cubes) into large‐area, free‐standing 2D and 3D superlattices. This robust approach involves two major steps: (i) the organization of polymer‐tethered NPs within the assemblies of supramolecular comblike block copolymers (CBCPs), and (ii) the disassembly of the assembled CBCP structures to produce free‐standing NP superlattices. It is demonstrated that the crystal structures and lattice constants of the superlattices can be readily tailored by varying the molecular weight of tethered polymers, the volume fraction of NPs, and the matrix of CBCPs. This template‐free approach may open a new avenue for the assembly of NPs into 2D and 3D structures with a wide range of potential applications.     

Reconfigurable Chiral Self‐Assembly of Peptides through Control of Terminal Charges

Self‐assembly of chiral nanostructures is of considerable interest, since the ability to control the chirality of these structures has direct ramifications in biology and materials science. A new approach to design chiral nanostructures from self‐assembly of N‐(9‐fluorenylmethoxycarbonyl)‐protected phenylalanine‐tryptophan‐lysine tripeptides is reported. The terminal charges can induce helical twisting of the assembled β‐sheets, enabling the formation of well‐defined chiral nanostructures. The degree and direction of twisting in the β‐sheets can be precisely tailored through in situ pH and temperature modulations. This enables the assembly of reconfigurable chiral nanomaterials with easily adjustable size and handedness. These results offer new insight into the mechanism of helical twist formation, which may enable the precise assembly of highly dynamical materials with potential applications in biomedicine, chiroptics, and chiral sensing.     

Self‐Assembly of Functional Molecules into 1D Crystalline Nanostructures

Self‐assembled functional nanoarchitectures are employed as important nanoscale building blocks for advanced materials and smart miniature devices to fulfill the increasing needs of high materials usage efficiency, low energy consumption, and high‐performance devices. One‐dimensional (1D) crystalline nanostructures, especially molecule‐composed crystalline nanostructures, attract significant attention due to their fascinating infusion structure and functionality which enables the easy tailoring of organic molecules with excellent carrier mobility and crystal stability. In this review, we discuss the recent progress of 1D crystalline self‐assembled nanostructures of functional molecules, which include both a small molecule‐derived and a polymer‐based crystalline nanostructure. The basic principles of the molecular structure design and the process engineering of 1D crystalline nanostructures are also discussed. The molecular building blocks, self‐assembly structures, and their applications in optical, electrical, and photoelectrical devices are overviewed and we give a brief outlook on crucial issues that need to be addressed in future research endeavors.     

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.     

Architectural Design of Self‐Assembled Hollow Superstructures

Colloidal nanoparticle assemblies are widely designed and fabricated via various building blocks to enhance their intrinsic properties and potential applications. Self‐assembled hollow superstructures have been a focal point in nanotechnology for several decades and are likely to remain so for the foreseeable future. The novel properties of self‐assembled hollow superstructures stem from their effective spatial utilization. As such, a comprehensive appreciation of the interactive forces at play among individual building blocks is a prerequisite for designing and managing the self‐assembly process, toward the fabrication of optimal hollow nanoproducts. Herein, the emerging approaches to the fabrication of self‐assembled hollow superstructures, including hard‐templated, soft‐templated, self‐templated, and template‐free methods, are classified and discussed. The corresponding reinforcement mechanisms, such as strong ligand interaction strategies and extra‐capping strategies, are discussed in detail. Finally, possible future directions for the construction of multifunctional hollow superstructures with highly efficient catalytic reaction systems and an integration platform for bioapplications are discussed.     

Self‐Assembly of Hyperbranched Polymers and Its Biomedical Applications

Hyperbranched polymers (HBPs) are highly branched macromolecules with a three‐dimensional dendritic architecture. Due to their unique topological structure and interesting physical/chemical properties, HBPs have attracted wide attention from both academia and industry. In this paper, the recent developments in HBP self‐assembly and their biomedical applications have been comprehensively reviewed. Many delicate supramolecular structures from zero‐dimension (0D) to three‐dimension (3D), such as micelles, fibers, tubes, vesicles, membranes, large compound vesicles and physical gels, have been prepared through the solution or interfacial self‐assembly of amphiphilic HBPs. In addition, these supramolecular structures have shown promising applications in the biomedical areas including drug delivery, protein purification/detection/delivery, gene transfection, antibacterial/antifouling materials and cytomimetic chemistry. Such developments promote the interdiscipline researches among surpramolecular chemistry, biomedical chemistry, nano­technology and functional materials.     

Supramolecular Helices: Chirality Transfer from Conjugated Molecules to Structures

Different scales of chirality endow a material with many excellent properties and potential applications. In this review, using π‐conjugated molecules as functional building blocks, recent progress on supramolecular helices inspired by biological helicity is summarized. First, induced chirality on conjugated polymers and small molecules is introduced. Molecular chirality can be amplified to nanostructures, superstructures, and even macroscopic structures by a self‐assembly process. Then, the principles for tuning the helicity of supramolecular chirality, as well as formation of helical heterojunctions, are summarized. Finally, the potential applications of chiral structures in chiral sensing and organic electronic devices are critically reviewed. Due to recent progress in chiral structures, an interdisciplinary area called “chiral electronics” is expected to gain wide popularity in the near future.     

Dynamic Self‐Assembly of Homogenous Microcyclic Structures Controlled by a Silver‐Coated Nanopore

The self‐assembly of nanoparticles is a challenging process for organizing precise structures with complicated and ingenious structures. In the past decades, a simple, high‐efficiency, and reproducible self‐assembly method from nanoscale to microscale has been pursued because of the promising and extensive application prospects in bioanalysis, catalysis, photonics, and energy storage. However, microscale self‐assembly still faces big challenges including improving the stability and homogeneity as well as pursuing new assembly methods and templates for the uniform self‐assembly. To address these obstacles, here, a novel silver‐coated nanopore is developed which serves as a template for electrochemically generating microcyclic structures of gold nanoparticles at micrometers with highly homogenous size and remarkable reproducibility. Nanopore‐induced microcyclic structures are further applied to visualize the diffusion profile of ionic flux. Based on this novel strategy, a nanopore could potentially facilitate the delivery of assembled structures for many practical applications including drug delivery, cellular detection, catalysis, and plasmonic sensing.     

Self‐Assembled Peptide‐Based Nanomaterials for Biomedical Imaging and Therapy

Peptide‐based materials are one of the most important biomaterials, with diverse structures and functionalities. Over the past few decades, a self‐assembly strategy is introduced to construct peptide‐based nanomaterials, which can form well‐controlled superstructures with high stability and multivalent effect. More recently, peptide‐based functional biomaterials are widely utilized in clinical applications. However, there is no comprehensive review article that summarizes this growing area, from fundamental research to clinic translation. In this review, the recent progress of peptide‐based materials, from molecular building block peptides and self‐assembly driving forces, to biomedical and clinical applications is systematically summarized. Ex situ and in situ constructed nanomaterials based on functional peptides are presented. The advantages of intelligent in situ construction of peptide‐based nanomaterials in vivo are emphasized, including construction strategy, nanostructure modulation, and biomedical effects. This review highlights the importance of self‐assembled peptide nanostructures for nanomedicine and can facilitate further knowledge and understanding of these nanosystems toward clinical translation.     

Biocatalytically Triggered Co‐Assembly of Two‐Component Core/Shell Nanofibers

For the development of applications and novel uses for peptide nanostructures, robust routes for their surface functionalization, that ideally do not interfere with their self‐assembly properties, are required. Many existing methods rely on covalent functionalization, where building blocks are appended with functional groups, either pre‐ or post‐assembly. A facile supramolecular approach is demonstrated for the formation of functionalized nanofibers by combining the advantages of biocatalytic self‐assembly and surfactant/gelator co‐assembly. This is achieved by enzymatically triggered reconfiguration of free flowing micellar aggregates of pre‐gelators and functional surfactants to form nanofibers that incorporate and display the surfactants’ functionality at the surface. Furthermore, by varying enzyme concentration, the gel stiffness and supramolecular organization of building blocks can be varied.