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.     

Self‐Assembled Peptide‐ and Protein‐Based Nanomaterials for Antitumor Photodynamic and Photothermal Therapy

Tremendous interest in self‐assembly of peptides and proteins towards functional nanomaterials has been inspired by naturally evolving self‐assembly in biological construction of multiple and sophisticated protein architectures in organisms. Self‐assembled peptide and protein nanoarchitectures are excellent promising candidates for facilitating biomedical applications due to their advantages of structural, mechanical, and functional diversity and high biocompability and biodegradability. Here, this review focuses on the self‐assembly of peptides and proteins for fabrication of phototherapeutic nanomaterials for antitumor photodynamic and photothermal therapy, with emphasis on building blocks, non‐covalent interactions, strategies, and the nanoarchitectures of self‐assembly. The exciting antitumor activities achieved by these phototherapeutic nanomaterials are also discussed in‐depth, along with the relationships between their specific nanoarchitectures and their unique properties, providing an increased understanding of the role of peptide and protein self‐assembly in improving the efficiency of photodynamic and photothermal therapy.     

Self‐Assembled α‐Cyanostilbenes for Advanced Functional Materials

In the specific context of condensed media, the significant and increasing recent interest in the α‐cyanostilbene (CS) motif [? Ar? CH?C(CN)? Ar? ] is relevant. These compounds have shown remarkable optical features in addition to interesting electrical properties, and hence they are recognized as very suitable and versatile options for the development of functional materials. This progress report is focused on current and future use of CS structures and molecular assemblies with the aim of exploring and developing for the next generations of functional materials. A critical selection of illustrative materials that contain the CS motif, including relevant subfamilies such as the dicyanodistyrylbenzene and 2,3,3‐triphenylacrylonitrile shows how, driven by the self‐assembly of CS blocks, a variety of properties, effects, and possibilities for practical applications can be offered to the scientific community, through different rational routes for the elaboration of advanced materials. A survey is provided on the research efforts directed toward promoting the self‐assembly of the solid state (polycrystalline solids, thin films, and single crystals), liquid crystals, nanostructures, and gels with multistimuli responsiveness, and applications for sensors, organic light‐emitting diodes, organic field effect transistors, organic lasers, solar cells, or bioimaging purposes.     

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.     

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.     

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.     

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.     

Bioinspired Peptoid Nanotubes for Targeted Tumor Cell Imaging and Chemo‐Photodynamic Therapy

Substantial progress has been made in applying nanotubes in biomedical applications such as bioimaging and drug delivery due to their unique architecture, characterized by very large internal surface areas and high aspect ratios. However, the biomedical applications of organic nanotubes, especially for those assembled from sequence‐defined molecules, are very uncommon. In this paper, the synthesis of two new peptoid nanotubes (PepTs1 and PepTs2) is reported by using sequence‐defined and ligand‐tagged peptoids as building blocks. These nanotubes are highly robust due to sharing a similar structure to those of nontagged ones, and offer great potential to hold guest molecules for biomedical applications. The findings indicate that peptoid nanotubes loaded with doxorubicin drugs are promising candidates for targeted tumor cell imaging and chemo‐photodynamic therapy.     

Beta‐Sheet‐Forming,Self‐Assembled Peptide Nanomaterials towards Optical,Energy, and Healthcare Applications

Peptide self‐assembly is an attractive route for the synthesis of intricate organic nanostructures that possess remarkable structural variety and biocompatibility. Recent studies on peptide‐based, self‐assembled materials have expanded beyond the construction of high‐order architectures; they are now reporting new functional materials that have application in the emerging fields such as artificial photosynthesis and rechargeable batteries. Nevertheless, there have been few reviews particularly concentrating on such versatile, emerging applications. Herein, recent advances in the synthesis of self‐assembled peptide nanomaterials (e.g., cross β‐sheet‐based amyloid nanostructures, peptide amphiphiles) are selectively reviewed and their new applications in diverse, interdisciplinary fields are described, ranging from optics and energy storage/conversion to healthcare. The applications of peptide‐based self‐assembled materials in unconventional fields are also highlighted, such as photoluminescent peptide nanostructures, artificial photosynthetic peptide nanomaterials, and lithium‐ion battery components. The relation of such functional materials to the rapidly progressing biomedical applications of peptide self‐assembly, which include biosensors/chips and regenerative medicine, are discussed. The combination of strategies shown in these applications would further promote the discovery of novel, functional, small materials.     

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.     

Directed Self‐Assembly of Liquid‐Crystalline Molecular Building Blocks for Sub‐5 nm Nanopatterning

The thin‐film directed self‐assembly of molecular building blocks into oriented nanostructure arrays enables next‐generation lithography at the sub‐5 nm scale. Currently, the fabrication of inorganic arrays from molecular building blocks is restricted by the limited long‐range order and orientation of the materials, as well as suitable methodologies for creating lithographic templates at sub‐5 nm dimensions. In recent years, higher‐order liquid crystals have emerged as functional thin films for organic electronics, nanoporous membranes, and templated synthesis, which provide opportunities for their use as lithographic templates. By choosing examples from these fields, recent progress toward the design of molecular building blocks is highlighted, with an emphasis on liquid crystals, to access sub‐5 nm features, their directed self‐assembly into oriented thin films, and, importantly, the fabrication of inorganic arrays. Finally, future challenges regarding sub‐5 nm patterning with liquid crystals are discussed.     

Assembling DNA into Advanced Materials: From Nanostructured Films to Biosensing and Delivery Systems

The past decade has witnessed a rapid expansion in the design and assembly of engineered materials for biological applications. However, such applications place limitations on the molecular building blocks that can be used. Requirements for polymer‐based building blocks include biocompatibility, biodegradability, and stimuli‐responsive behavior. Many traditional polymers used in materials science are limited in at least one of these areas, so new polymers need to be explored. As we outline here, DNA is one such polymer that shows promise in developing the next generation of ‘smart’ materials for biomedical and diagnostic applications.     

Guiding the Morphology of Amyloid Assemblies by Electrostatic Capping: from Polymorphic Twisted Fibrils to Uniform Nanorods

Peptides that self‐assemble into cross‐β‐sheet amyloid structures constitute promising building blocks to construct highly ordered proteinaceous materials and nanoparticles. Nevertheless, the intrinsic polymorphism of amyloids and the difficulty of controlling self‐assembly currently limit their usage. In this study, the effect of electrostatic interactions on the supramolecular organization of peptide assemblies is investigated to gain insights into the structural basis of the morphological diversities of amyloids. Different charged capping units are introduced at the N‐terminus of a potent β‐sheet‐forming sequence derived from the 20–29 segment of islet amyloid polypeptide, known to self‐assemble into polymorphic fibrils. By tuning the charge and the electrostatic strength, different mesoscopic morphologies are obtained, including nanorods, rope‐like fibrils, and twisted ribbons. Particularly, the addition of positive capping units leads to the formation of uniform rod‐like assemblies, with lengths that can be modulated by the charge number. It is proposed that electrostatic repulsions between N‐terminal positive charges hinder β‐sheet tape twisting, leading to a unique control over the size of these cytocompatible nanorods by protofilament growth frustration. This study reveals the high susceptibility of amyloid formation to subtle chemical modifications and opens to promising strategies to control the final architecture of proteinaceous assemblies from the peptide sequence.     

Morphosynthesis of Molecular Magnetic Materials

Although molecule‐based materials can combine physical and chemical properties associated with molecular‐scale building blocks, their successful integration into real applications depends also on higher‐order properties, such as crystal size, shape, and organization. New approaches involving templating and self‐ or facilitated assembly of nanoscale building blocks to prepare novel multifunctional molecular magnetic materials with complex form and organization are described.     

Effective Light Directed Assembly of Building Blocks with Microscale Control

Light‐directed forces have been widely used to pattern micro/nanoscale objects with precise control, forming functional assemblies. However, a substantial laser intensity is required to generate sufficient optical gradient forces to move a small object in a certain direction, causing limited throughput for applications. A high‐throughput light‐directed assembly is demonstrated as a printing technology by introducing gold nanorods to induce thermal convection flows that move microparticles (diameter = 40 µm to several hundreds of micrometers) to specific light‐guided locations, forming desired patterns. With the advantage of effective light‐directed assembly, the microfluidic‐fabricated monodispersed biocompatible microparticles are used as building blocks to construct a structured assembly (≈10 cm scale) in ≈2 min. The control with microscale precision is approached by changing the size of the laser light spot. After crosslinking assembly of building blocks, a novel soft material with wanted pattern is approached. To demonstrate its application, the mesenchymal stem‐cell‐seeded hydrogel microparticles are prepared as functional building blocks to construct scaffold‐free tissues with desired structures. This light‐directed fabrication method can be applied to integrate different building units, enabling the bottom‐up formation of materials with precise control over their internal structure for bioprinting, tissue engineering, and advanced manufacturing.     

Modulating the Mechanical Performance of Macroscale Fibers through Shear‐Induced Alignment and Assembly of Protein Nanofibrils

Protein‐based fibers are used by nature as high‐performance materials in a wide range of applications, including providing structural support, creating thermal insulation, and generating underwater adhesives. Such fibers are commonly generated through a hierarchical self‐assembly process, where the molecular building blocks are geometrically confined and aligned along the fiber axis to provide a high level of structural robustness. Here, this approach is mimicked by using a microfluidic spinning method to enable precise control over multiscale order during the assembly process of nanoscale protein nanofibrils into micro‐ and macroscale fibers. By varying the flow rates on chip, the degree of nanofibril alignment can be tuned, leading to an orientation index comparable to that of native silk. It is found that the Young's modulus of the resulting fibers increases with an increasing level of nanoscale alignment of the building blocks, suggesting that the mechanical properties of macroscopic fibers can be controlled through varying the level of ordering of the nanoscale building blocks. Capitalizing on strategies evolved by nature, the fabrication method allows for the controlled formation of macroscopic fibers and offers the potential to be applied for the generation of further novel bioinspired materials.     

Biomimetic Design of Hollow Flower‐Like g‐C3N4@PDA Organic Framework Nanospheres for Realizing an Efficient Photoreactivity

Organic framework polymers have attracted much interest due to the enormous potential design space offered by the atomically precise spatial assembly of organic molecular building blocks. The morphology control of organic frameworks is a complex issue that hinders the development of organic frameworks for practical applications. Biomimetic self‐assembly is a promising approach for designing and fabricating multiple‐functional nanoarchitectures. A bioinspired hollow flower‐like organic framework nanosphere heterostructure comprised of carbon nitride and polydopamine (g‐C3N4@PDA) is successfully synthesized via a mild and green method. This heterostructure can effectively avoid the agglomeration of nanosheets to better access the hollow nanospheres with high open‐up specific surface area. The electron delocalization of g‐C3N4 and PDA under visible light can largely promote photoelectron transfer and enhance the photocatalytic activity of the g‐C3N4@PDA. Furthermore, the g‐C3N4@PDA can effectively enhance the generation of reactive oxygen species under irradiation, which can lead to cell apoptosis and enhance the performance for cancer therapy. Therefore, the as‐prepared g‐C3N4@PDA provides a paradigm of highly efficient photocatalyst that can be used as nanomedicine toward cancer therapy. This study could open up a new avenue for exploiting more other potential hollow nanosphere organic frameworks.     

Photoacoustic Imaging: Contrast Agents and Their Biomedical Applications

Photoacoustic (PA) imaging as a fast‐developing imaging technique has great potential in biomedical and clinical applications. It is a noninvasive imaging modality that depends on the light‐absorption coefficient of the imaged tissue and the injected PA‐imaging contrast agents. Furthermore, PA imaging provides superb contrast, super spatial resolution, and high penetrability and sensitivity to tissue functional characteristics by detecting the acoustic wave to construct PA images. In recent years, a series of PA‐imaging contrast agents are developed to improve the PA‐imaging performance in biomedical applications. Here, recent progress of PA contrast agents and their biomedical applications are outlined. PA contrast agents are classified according to their components and function, and gold nanocrystals, gold‐nanocrystal assembly, transition‐metal chalcogenides/MXene‐based nanomaterials, carbon‐based nanomaterials, other inorganic imaging agents, small organic molecules, semiconducting polymer nanoparticles, and nonlinear PA‐imaging contrast agents are discussed. The applications of PA contrast agents as biosensors (in the sensing of metal ions, pH, enzymes, temperature, hypoxia, reactive oxygen species, and reactive nitrogen species) and in bioimaging (lymph nodes, vasculature, tumors, and brain tissue) are discussed in detail. Finally, an outlook on the future research and investigation of PA‐imaging contrast agents and their significance in biomedical research is presented.     

Self‐Correction Strategy for Precise,Massive, and Parallel Macroscopic Supramolecular Assembly

Macroscopic supramolecular assembly (MSA) represents a new advancement in supramolecular chemistry involving building blocks with sizes beyond tens of micrometers associating through noncovalent interactions. MSA is established as a unique method to fabricate supramolecularly assembled materials by shortening the length scale between bulk materials and building blocks. However, improving the precise alignment during assembly to form orderly assembled structures remains a challenge. Although the pretreatment of building blocks can ameliorate order to a certain degree, defects or mismatching still exists, which limits the practical applications of MSA. Therefore, an iterative poststrategy is proposed, where self‐correction based on dynamic assembly/disassembly is applied to achieve precise, massive, and parallel assembly. The self‐correction process consists of two key steps: the identification of poorly ordered structures and the selective correction of these structures. This study develops a diffusion‐kinetics‐dependent disassembly to well identify the poorly aligned structures and correct these structures through iterations of disassembly/reassembly in a programmed fashion. Finally, a massive and parallel assembly of 100 precise dimers over eight iteration cycles is achieved, thus providing a powerful solution to the problem of processing insensitivity to errors in self‐assembly‐related methods.