Two‐Dimensional Nanomaterials for Biomedical Applications: Emerging Trends and Future Prospects

Two‐dimensional (2D) nanomaterials are ultrathin nanomaterials with a high degree of anisotropy and chemical functionality. Research on 2D nanomaterials is still in its infancy, with the majority of research focusing on elucidating unique material characteristics and few reports focusing on biomedical applications of 2D nanomaterials. Nevertheless, recent rapid advances in 2D nanomaterials have raised important and exciting questions about their interactions with biological moieties. 2D nanoparticles such as carbon‐based 2D materials, silicate clays, transition metal dichalcogenides (TMDs), and transition metal oxides (TMOs) provide enhanced physical, chemical, and biological functionality owing to their uniform shapes, high surface‐to‐volume ratios, and surface charge. Here, we focus on state‐of‐the‐art biomedical applications of 2D nanomaterials as well as recent developments that are shaping this emerging field. Specifically, we describe the unique characteristics that make 2D nanoparticles so valuable, as well as the biocompatibility framework that has been investigated so far. Finally, to both capture the growing trend of 2D nanomaterials for biomedical applications and to identify promising new research directions, we provide a critical evaluation of potential applications of recently developed 2D nanomaterials.     

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.     

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.     

Nanomaterial‐Enabled Stretchable Conductors: Strategies,Materials and Devices

Stretchable electronics are attracting intensive attention due to their promising applications in many areas where electronic devices undergo large deformation and/or form intimate contact with curvilinear surfaces. On the other hand, a plethora of nanomaterials with outstanding properties have emerged over the past decades. The understanding of nanoscale phenomena, materials, and devices has progressed to a point where substantial strides in nanomaterial‐enabled applications become realistic. This review summarizes recent advances in one such application, nanomaterial‐enabled stretchable conductors (one of the most important components for stretchable electronics) and related stretchable devices (e.g., capacitive sensors, supercapacitors and electroactive polymer actuators), over the past five years. Focusing on bottom‐up synthesized carbon nanomaterials (e.g., carbon nanotubes and graphene) and metal nanomaterials (e.g., metal nanowires and nanoparticles), this review provides fundamental insights into the strategies for developing nanomaterial‐enabled highly conductive and stretchable conductors. Finally, some of the challenges and important directions in the area of nanomaterial‐enabled stretchable conductors and devices are discussed.     

Two‐Dimensional Arrays of Transition Metal Nitride Nanocrystals

The synthesis of low‐dimensional transition metal nitride (TMN) nanomaterials is developing rapidly, as their fundamental properties, such as high electrical conductivity, lead to many important applications. However, TMN nanostructures synthesized by traditional strategies do not allow for maximum conductivity and accessibility of active sites simultaneously, which is a crucial factor for many applications in plasmonics, energy storage, sensing, and so on. Unique interconnected two‐dimensional (2D) arrays of few‐nanometer TMN nanocrystals not only having electronic conductivity in‐plane, but also allowing transport of ions and electrolyte through the porous nanosheets, which are obtained by topochemical synthesis on the surface of a salt template, are reported. As a demonstration of their application in a lithium–sulfur battery, it is shown that 2D arrays of several nitrides can achieve a high initial capacity of >1000 mAh g^?1 at 0.2 C and only about 13% degradation over 1000 cycles at 1 C under a high areal sulfur loading (>5 mg cm^?2).     

25th Anniversary Article: Hybrid Nanostructures Based on Two‐Dimensional Nanomaterials

Two‐dimensional (2D) nanomaterials, such as graphene and transition metal dichalcogenides (TMDs), receive a lot of attention, because of their intriguing properties and wide applications in catalysis, energy‐storage devices, electronics, optoelectronics, and so on. To further enhance the performance of their application, these 2D nanomaterials are hybridized with other functional nanostructures. In this review, the latest studies of 2D nanomaterial‐based hybrid nanostructures are discussed, focusing on their preparation methods, properties, and applications.     

Multifunctional Photonic Nanomaterials for Diagnostic,Therapeutic, and Theranostic Applications

The last decade has seen dramatic progress in the principle, design, and fabrication of photonic nanomaterials with various optical properties and functionalities. Light‐emitting and light‐responsive nanomaterials, such as semiconductor quantum dots, plasmonic metal nanoparticles, organic carbon, and polymeric nanomaterials, offer promising approaches to low‐cost and effective diagnostic, therapeutic, and theranostic applications. Reasonable endeavors have begun to translate some of the promising photonic nanomaterials to the clinic. Here, current research on the state‐of‐the‐art and emerging photonic nanomaterials for diverse biomedical applications is reviewed, and the remaining challenges and future perspectives are discussed.     

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.     

Self‐Assembling Endogenous Biliverdin as a Versatile Near‐Infrared Photothermal Nanoagent for Cancer Theranostics

Photothermal nanomaterials that integrate multimodal imaging and therapeutic functions provide promising opportunities for noninvasive and targeted diagnosis and treatment in precision medicine. However, the clinical translation of existing photothermal nanoagents is severely hindered by their unclear physiological metabolism, which makes them a strong concern for biosafety. Here, the utilization of biliverdin (BV), an endogenic near‐infrared (NIR)‐absorbing pigment with well‐studied metabolic pathways, to develop photothermal nanoagents with the aim of providing efficient and metabolizable candidates for tumor diagnosis and therapy, is demonstrated. It is shown that BV nanoagents with intense NIR absorption, long‐term photostability and colloidal stability, and high photothermal conversion efficiency can be readily constructed by the supramolecular multicomponent self‐assembly of BV, metal‐binding short peptides, and metal ions through the reciprocity and synergy of coordination and multiple noncovalent interactions. In vivo data reveal that the BV nanoagents selectively accumulate in tumors, locally elevate tumor temperature under mild NIR irradiation, and consequently induce efficient photothermal tumor ablation with promising biocompatibility. Furthermore, the BV nanoagents can serve as a multimodal contrast for tumor visualization through both photoacoustic and magnetic resonance imaging. BV has no biosafety concerns, and thereby offers a great potential in precision medicine by integrating multiple theranostic functions.     

Toxicity of Metal Oxide Nanoparticles: Mechanisms,Characterization, and Avoiding Experimental Artefacts

Metal oxide nanomaterials are widely used in practical applications and represent a class of nanomaterials with the highest global annual production. Many of those, such as TiO₂ and ZnO, are generally considered non‐toxic due to the lack of toxicity of the bulk material. However, these materials typically exhibit toxicity to bacteria and fungi, and there have been emerging concerns about their ecotoxicity effects. The understanding of the toxicity mechanisms is incomplete, with different studies often reporting contradictory results. The relationship between the material properties and toxicity appears to be complex and diifficult to understand, which is partly due to incomplete characterization of the nanomaterial, and possibly due to experimental artefacts in the characterization of the nanomaterial and/or its interactions with living organisms. This review discusses the comprehensive characterization of metal oxide nanomaterials and the mechanisms of their toxicity.     

High‐Yield Synthesis of Crystal‐Phase‐Heterostructured 4H/fcc Au@Pd Core–Shell Nanorods for Electrocatalytic Ethanol Oxidation

Noble‐metal nanomaterials are attracting increasing research interest due to their promising applications in electrochemical catalysis, for example. Although great efforts have been devoted to the size‐, shape‐, and architecture‐controlled synthesis of noble‐metal nanomaterials, their crystal‐phase‐controlled synthesis is still in its infancy. Here, for the first time, this study reports high‐yield synthesis of Au nanorods (NRs) with alternating 4H/face‐centered cubic (fcc) crystal‐phase heterostructures via a one‐pot wet‐chemical method. The coexistence of 4H and fcc phases is relatively stable, and the 4H/fcc Au NRs can serve as templates for crystal‐phase‐controlled epitaxial growth of other metals. As an example, bimetallic 4H/fcc Au@Pd core–shell NRs are synthesized via the epitaxial growth of Pd on 4H/fcc Au NRs. Significantly, the 4H/fcc Au@Pd NRs show superior mass activity toward the ethanol oxidation reaction, i.e., 6.2 and 4.9 times those of commercial Pd black and Pt/C catalysts, respectively. It is believed that this new synthetic strategy can be used to prepare other novel catalysts for various promising applications.     

Colloidally Stable Monolayer Nanosheets with Colorimetric Responses

Despite the discovery of chromogenic‐layered materials for decades of years, fabrication of colloidally stable monolayer organic 2D nanosheets in aqueous media with colorimetric responses is still challenging. Herein reported is the first solution synthesis of chromic monolayer nanosheets via the topochemical polymerization of self‐assembled amphiphilic diacetylenes in aqueous media. The polydiacetylene (PDA) nanosheets are ≈3–4 nm thick in solution and only ≈1.9 nm thick in the dried state, while the lateral size can reach several micrometers. Moreover, the aqueous stability endows PDA nanosheets with excellent processability, which can further assemble into films via vacuum filtration or act as an ink for high‐resolution inkjet printing. The filtrated films and printed patterns exhibit fully reversible blue‐to‐red thermochromism, and the film also displays an interesting reversible colorimetric transition in response to near‐infrared light, which is not reported for other PDA‐only systems. The present colloidal PDA nanosheets should represent a new kind of chromic organic 2D nanomaterials that may be applied as novel building blocks for developing intelligent hybrid materials and may also find diverse sensing, display and/or anticounterfeiting applications.     

Microfluidic Platforms toward Rational Material Fabrication for Biomedical Applications

The emergence of micro/nanomaterials in recent decades has brought promising alternative approaches in various biomedicine‐related fields such as pharmaceutics, diagnostics, and therapeutics. These micro/nanomaterials for specific biomedical applications shall possess tailored properties and functionalities that are closely correlated to their geometries, structures, and compositions, therefore placing extremely high demands for manufacturing techniques. Owing to the superior capabilities in manipulating fluids and droplets at microscale, microfluidics has offered robust and versatile platform technologies enabling rational design and fabrication of micro/nanomaterials with precisely controlled geometries, structures and compositions in high throughput manners, making them excellent candidates for a variety of biomedical applications. This review briefly summarizes the progress of microfluidics in the fabrication of various micro/nanomaterials ranging from 0D (particles), 1D (fibers) to 2D/3D (film and bulk materials) materials with controllable geometries, structures, and compositions. The applications of these microfluidic‐based materials in the fields of diagnostics, drug delivery, organs‐on‐chips, tissue engineering, and stimuli‐responsive biodevices are introduced. Finally, an outlook is discussed on the future direction of microfluidic platforms for generating materials with superior properties and on‐demand functionalities. The integration of new materials and techniques with microfluidics will pave new avenues for preparing advanced micro/nanomaterials with enhanced performance for biomedical applications.     

Ultrathin Two‐Dimensional Multinary Layered Metal Chalcogenide Nanomaterials

Ultrathin two‐dimensional (2D) layered transition metal dichalcogenides (TMDs), such as MoS₂, WS₂, TiS₂, TaS₂, ReS₂, MoSe₂ and WSe₂, have attracted considerable attention over the past six years owing to their unique properties and great potential in a wide range of applications. Aiming to achieve tunable properties and optimal application performances, great effort is devoted to the exploration of 2D multinary layered metal chalcogenide nanomaterials, which include ternary metal chalcogenides with well‐defined crystal structures, alloyed TMDs, heteroatom‐doped TMDs and 2D metal chalcogenide heteronanostructures. These novel 2D multinary layered metal chalcogenide nanomaterials exhibit some unique properties compared to 2D binary TMD counterparts, thus holding great promise in various potential applications including electronics/optoelectronics, catalysis, sensors, biomedicine, and energy storage and conversion with enhanced performances. This article focuses on the state‐of‐art progress on the preparation, characterization and applications of ultrathin 2D multinary layered metal chalcogenide nanomaterials.     

Nano‐Biohybrids: In Vivo Synthesis of Metal–Organic Frameworks inside Living Plants

Plants have a complex passive fluid transport system capable of internalizing small molecules from the environment, and this system offers an ideal route for augmenting plants with functional nanomaterials. Current plant augmentation techniques use pre‐formed nanomaterials and permeabilizing agents or plant cuttings. A so far unexplored concept is the formation of the functional material, in situ, from precursors small enough to be passively internalized through the roots without harming the plants. Metal–organic frameworks are ideal for in situ synthesis as they are composed of metal ions coordinated with organic ligands and have recently been mineralized around single‐celled organisms in mild aqueous conditions. Herein, the synthesis of two types of metal‐organic frameworks, zinc(2‐methylimidazole)₂ and lanthanide₂(terephthalate)₃, are reported inside a variety of plants. In situ synchrotron experiments help elucidate the formation kinetics and crystal phases of the nano‐biohybrid plants. Plants augmented with luminescent metal‐organic frameworks are utilized for small molecule sensing, although other applications, such as pathogen sensing, proton conductive plants, improved CO₂ capture, bacteria‐free nitrogen fixation, drought and fungi‐resistance, and enhanced photosynthesis and photocatalysis, are foreseeable. Overall, the generation of functional materials inside of fully intact plants could lead to more complex nano‐biohybrid sensors and organisms augmented with superior performance characteristics.     

Multivalent Interactions between 2D Nanomaterials and Biointerfaces

2D nanomaterials, particularly graphene, offer many fascinating physicochemical properties that have generated exciting visions of future biological applications. In order to capitalize on the potential of 2D nanomaterials in this field, a full understanding of their interactions with biointerfaces is crucial. The uptake pathways, toxicity, long‐term fate of 2D nanomaterials in biological systems, and their interactions with the living systems are fundamental questions that must be understood. Here, the latest progress is summarized, with a focus on pathogen, mammalian cell, and tissue interactions. The cellular uptake pathways of graphene derivatives will be discussed, along with health risks, and interactions with membranes—including bacteria and viruses—and the role of chemical structure and modifications. Other novel 2D nanomaterials with potential biomedical applications, such as transition‐metal dichalcogenides, transition‐metal oxide, and black phosphorus will be discussed at the end of this review.     

Carbon‐Based Metal‐Free Catalysts for Energy Storage and Environmental Remediation

Owing to their high earth‐abundance, eco‐friendliness, high electrical conductivity, large surface area, structure tunability at the atomic/morphological levels, and excellent stability in harsh conditions, carbon‐based metal‐free materials have become promising advanced electrode materials for high‐performance pseudocapacitors and metal–air batteries. Furthermore, carbon‐based nanomaterials with well‐defined structures can function as green catalysts because of their efficiency in advanced oxidation processes to remove organics in air or from water, which reduces the cost for air/water purification and avoids cross‐contamination by eliminating the release of heavy metals/metal ions. Here, the research and development of carbon‐based catalysts in supercapacitors and batteries for clean energy storage as well as in air/water treatments for environmental remediation are reviewed. The related mechanistic understanding and design principles of carbon‐based metal‐free catalysts are illustrated, along with the challenges and perspectives in this emerging field.     

Light‐Induced Shape Morphing of Liquid Metal Nanodroplets Enabled by Polydopamine Coating

Shape morphing nanosystems have recently attracted much attention and a number of applications are developed, spanning from autonomous robotics to drug delivery. However, the fabrication of such nanosystems remains at an early stage owing to limited choices of strategies and materials. This work reports a facile method to fabricate liquid metal (LM) nanodroplets by sonication of bulk LM in an aqueous dopamine hydrochloride solution and their application in light‐induced shape morphing at the nanoscale. In this method, dopamine acts as a surfactant, which stabilizes the LM nanodroplets dispersion during the sonication, and results in downsizing of the nanodroplets. Furthermore, by adding 2‐amino‐2‐(hydroxymethyl)‐1,3‐propanediol to the suspension, self‐polymerization of dopamine molecules occurs, resulting in the formation of polydopamine (PDA)‐coated LM nanodroplets. Owing to the high photothermal conversion of the PDA, PDA‐coated LM nanodroplets are transformed from spherical shapes to ellipsoids by NIR laser irradiation. This study paves a simple and reliable pathway for the preparation of functional LM nanodroplets and their application as shape‐morphing nanosystems.     

From Galvanic to Anti‐Galvanic Synthesis of Bimetallic Nanoparticles and Applications in Catalysis,Sensing, and Materials Science

The properties of two alloyed metals have been known since the Bronze Age to outperform those of a single metal. How alloying and mixing metals applies to the nanoworld is now attracting considerable attention. The galvanic process, which is more than two centuries old and involves the reduction of a noble‐metal cation by a less noble metal, has not only been used in technological processes, but also in the design of nanomaterials for the synthesis of bimetallic transition‐metal nanoparticles. The background and nanoscience applications of the galvanic reactions (GRs) are reviewed here, in particular with emphasis on recent progress in bimetallic catalysis. Very recently, new reactions have been discovered with nanomaterials that contradict the galvanic principle, and these reactions, called anti‐galvanic reactions (AGRs), are now attracting much interest for their mechanistic, synthetic, catalytic, and sensor aspects. The second part of the review deals with these AGRs and compares GRs and AGRs, including the intriguing AGRs mechanism and the first applications.     

One Dimensional Silver‐based Nanomaterials: Preparations and Electrochemical Applications

One dimensional (1D) silver‐based nanomaterials have a great potential in various fields because of their high specific surface area, high electric conductivity, optoelectronic properties, mechanical flexibility and high electro‐catalytic efficiency. In this Review, the preparations of 1D silver‐based nanomaterials is classified by structure composed of simple silver nanowires/rods/belts/tubes, core‐shells, and hybrids. The latest applications based on 1D silver nanomaterials and their composite materials are summarized systematically including electrochemical capacitors, lithium‐ion/lithium‐oxygen batteries, electrochemical sensors and electrochemical catalysis. The preparation process, tailored material properties and electrochemical applications are discussed.