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Synthetic cell exoskeletons created from abiotic materials have attracted interest in materials science and biotechnology, as they can regulate cell behavior and create new functionalities. Here, a facile strategy is reported to mimic microalgal sporulation with on-demand germination and locomotion via responsive metal-phenolic networks (MPNs). Specifically, MPNs with tunable thickness and composition are deposited on the surface of microalgae cells via one-step coordination, without any loss of cell viability or intrinsic cell photosynthetic properties. The MPN coating keeps the cells in a dormant state, but can be disassembled on-demand in response to environmental pH or chemical stimulus, thereby reviving the microalgae within 1 min. Moreover, the artificial sporulation of microalgae resulted in resistance to environmental stresses (e.g., metal ions and antibiotics) akin to the function of natural sporulation. This strategy can regulate the life cycle of complex cells, providing a synthetic strategy for designing hybrid microorganisms.

Crystalline metal-organic frameworks (MOFs) have garnered extensive attention owing to their highly ordered porous structure and physicochemical properties. However, their practical application often requires their integration with various substrates, which is challenging because of their weakly adhesive nature and the diversity of substrates that exhibit different properties. Herein, we report the use of amorphous metal-phenolic network coatings to facilitate the growth of crystalline MOF coatings on various particle and planar substrates. Crystalline MOFs with different metal ions and morphologies were successfully deposited on substrates (13 types) of varying sizes, shapes, and surface chemistries. Furthermore, the physicochemical properties of the coated crystalline MOFs (e.g., composition, thickness) could be tuned using different synthesis conditions. The engineered MOF-coated membranes demonstrated excellent liquid and gas separation performance, exhibiting a high H2 permeance of 63200 GPU and a H2/CH4 selectivity of 10.19, likely attributable to the thin nature of the coating (~180 nm). Considering the vast array of MOFs available (>90,000) and the diversity of substrates, this work is expected to pave the way for creating a wide range of MOF composites and coatings with potential applications in diverse fields.

Protocells have garnered considerable attention from cell biologists, materials scientists, and synthetic biologists. Phase-separating coacervate microdroplets have emerged as a promising cytomimetic model because they can internalize and concentrate components from dilute surrounding environments. However, the membrane-free nature of such coacervates leads to coalescence into a bulk phase, a phenomenon that is not representative of the cells they are designed to mimic. Herein, we develop a membranized peptide coacervate (PC) with oppositely charged oligopeptides as the molecularly crowded cytosol and a metal-phenolic network (MPN) coating as the membrane. The hybrid protocell efficiently internalizes various bioactive macromolecules (e.g., bovine serum albumin and immunoglobulin G) (>90%) while also resisting radicals due to the semipermeable cytoprotective membrane. Notably, the resultant PC@MPNs are capable of anabolic cascade reactions and remain in discrete protocellular populations without coalescence. Finally, we demonstrate that the MPN protocell membrane can be postfunctionalized with various functional molecules (e.g., folic acid and fluorescence dye) to more closely resemble actual cells with complex membranes, such as recognition molecules, which allows for drug delivery. This membrane-bound cytosolic protocell structure paves the way for innovative synthetic cells with structural and functional complexity.

Nanostructured materials with tunable structures and functionality are of interest in diverse areas. Herein, metal ions are coordinated with quinones through metal‐acetylacetone coordination bonds to generate a class of structurally tunable, universally adhesive, hydrophilic, and pH‐degradable materials. A library of metal‐quinone networks (MQNs) is produced from five model quinone ligands paired with nine metal ions, leading to the assembly of particles, tubes, capsules, and films. Importantly, MQNs show bidirectional pH‐responsive disassembly in acidic and alkaline solutions, where the quinone ligands mediate the disassembly kinetics, enabling temporal and spatial control over the release of multiple components using multilayered MQNs. Leveraging this tunable release and the inherent medicinal properties of quinones, MQN prodrugs with a high drug loading (>89 wt %) are engineered using doxorubicin for anti‐cancer therapy and shikonin for the inhibition of the main protease in the SARS‐CoV‐2 virus.

The stability and activity of electrocatalysts are fundamental in energy‐related applications (e.g., hydrogen generation and energy storage). Electrocatalysts degrade over time when the active centers are not strongly anchored to the support. However, if the active centers are too strongly anchored, the activity of the electrocatalysts decreases due to reduced accessibility to reactants. Herein, a strategy is presented to balance the stability and activity of different active materials using a natural and flexible support material that can be woven and carbonized. Lotus fibers, which have surface hydroxyl and phenolic groups, high mechanical strength, and a mesoscale porosity post‐pyrolysis, are used to load diverse functional metal‐containing materials such as metal–organic frameworks, 2D materials, metal sulfide nanoparticles, metal ions, and high‐entropy alloys. After pyrolysis, the electrocatalysts display flexibility, high catalytic performance, and long‐term stability, outperforming commercial benchmarks (e.g., Pt/C) in specific scenarios for water splitting, liquid batteries, and flexible electronics.

Coordination polymers (CPs) and their subset, metal-organic frameworks (MOFs), can have porous structures and hybrid physicochemical properties that are useful for diverse applications. Although crystalline CPs and MOFs have received the most attention to date, their amorphous states are of growing interest as they can be directly synthesized under mild conditions. Directly synthesized amorphous CPs (aCPs) can be constructed from a wider range of metals and ligands than their crystalline and crystal-derived counterparts and demonstrate numerous unique material properties, such as higher mechanical robustness, increased stability and greater processability. This Review examines methods for the direct synthesis of aCPs and amorphous MOFs, as well as their properties and characterization routes, and offers a perspective on the opportunities for the widespread adoption of directly synthesized aCPs.

Advanced treatments based on immune system manipulation, gene transcription and regulation, specific organ and cell targeting, and/or photon energy conversion have emerged as promising therapeutic strategies against a range of challenging diseases. Naturally derived macromolecules (e.g., proteins, lipids, polysaccharides, and polyphenols) have increasingly found use as fundamental building blocks for nanostructured particles as their advantageous properties, including biocompatibility, biodegradability, inherent bioactivity, and diverse chemical properties make them suitable for advanced therapeutic applications. This review provides a timely and comprehensive summary of the use of a broad range of natural building blocks in the rapidly developing field of advanced therapeutics with insights specific to nanostructured particles. We focus on an up-to-date overview of the assembly of nanostructured particles using natural building blocks and summarize their key scientific and preclinical milestones for advanced therapies, including adoptive cell therapy, immunotherapy, gene therapy, active targeted drug delivery, photoacoustic therapy and imaging, photothermal therapy, and combinational therapy. A cross-comparison of the advantages and disadvantages of different natural building blocks are highlighted to elucidate the key design principles for such bio-derived nanoparticles toward improving their performance and adoption. Current challenges and future research directions are also discussed, which will accelerate our understanding of designing, engineering, and applying nanostructured particles for advanced therapies.

The development of antimicrobial fabrics and textiles that can sustainably inhibit a broad spectrum of microbes is crucial for protecting against pathogens in various environments. However, engineering antimicrobial textiles is challenging due to issues with discoloration and inhibited breathability, the use of harmful or harsh reagents and synthesis conditions, and complex and/or time-consuming processing. Herein, we develop a facile and rapid approach to deposit antimicrobial coatings using universally adherent plant polyphenols and antimicrobial silver ions. Importantly, the coatings are colorless, thin (< 10 nm), rapidly assembled (< 20 min), and can be deposited via immersion or spraying. We demonstrate that these metal-phenolic coatings on textiles can inhibit lipid-enveloped viruses over one thousand times more efficiently than coatings composed of other metal ions, while maintaining their efficacy even after 5 washes. Moreover, the coatings also inhibit Gram positive and negative bacteria, and fungi, and can prevent odors on clothes for at least 10 washes. Collectively, the ease of synthesis, use of simple and safe precursors, and amenability to at-home and industrial application suggests that the coatings will find practical application in various settings.

Fluorinated motifs are promising for the engineering of repellent coatings, however, a fundamental understanding of how to effectively bind these motifs to various substrates is required to improve their stability in different use scenarios. Herein, the binding of fluorinated polyhedral oligomeric silsesquioxanes (POSS) using a cyanoacrylate glue (binder) is computationally and experimentally evaluated. The composite POSS-binder coatings display ultralow surface energy (≈10 mJ m-2 ), while still having large surface adhesions to substrates (300-400 nN), highlighting that super-repellent coatings (contact angles >150°) can be readily generated with this composite approach. Importantly, the coatings show super-repellency to both corrosive liquids (e.g., 98 wt% H2 SO4 ) and ultralow surface tension liquids (e.g., alcohols), with ultralow roll-off angles (<5°), and tunable resistance to liquid penetration. Additionally, these coatings demonstrate the potential in effective cargo loading and robust self-cleaning properties, where experimental datasets are correlated with both relevant theoretical predictions and systematic all-atom molecular dynamics simulations of the repellent coatings. This work not only holds promise for chemical shielding, heat transfer, and liquid manipulations but offers a facile yet robust pathway for engineering advanced coatings by effectively combining components for their mutually desired properties.

Robust underwater adhesion is challenging because a hydration layer impedes the interaction between substrates and adhesives. Phenolic adhesives inspired by marine creatures such as mussels were extensively studied, but these adhesives have not reached the adhesion strength and substrate diversity of Man-made dry adhesives. Here, we report a class of ultrastrong underwater adhesives with molecular phenolic designs extending beyond what nature has produced. These non-canonical phenolic polymers show versatile adhesion on various materials, with adhesion strengths exceeding 10 MPa on metal. Incorporating even just a small amount (<10%) of non-canonical phenolic groups into a polymer is sufficient for dramatically enhancing underwater adhesion, suggesting that this new class of phenolic materials will be incorporated into various industrial polymer systems in the future.

New materials for combating bacteria-caused infection and promoting the formation of microvascular networks during wound healing are of vital importance. Although antibiotics can be used to prevent infection, treatments that can disinfect and accelerate wound healing are scarce. Herein, we engineer a coating that is both highly compatible with current wound dressing substrates and capable of simultaneously disinfecting and revascularizing wounds using a metal-phenolic nanoplatform containing an alloyed nanostructured architecture (Ag@Cu-MPNNC). The alloyed nanostructure is formed by the spontaneous co-reduction and catalytic disproportionation reaction of multiple metal ions on a foundation metal-phenolic supramolecular layer. This synergistic presence of metals greatly improves the antibacterial activity against both Gram-negative and Gram-positive pathogenic bacteria, while demonstrating negligible cytotoxicity to normal tissue. In infected rat models, the Ag@Cu-MPNNC could kill bacteria efficiently, promoting revascularization and accelerate wound closure with no adverse side effects in infected in vivo models. In other words, this material acts as a combination therapy by inhibiting bacterial invasion and modulating bio-nano interactions in the wound.

The integration of bioactive materials (e.g., proteins and genes) into nanoparticles holds promise in fields ranging from catalysis to biomedicine. However, it is challenging to develop a simple and broadly applicable nanoparticle platform that can readily incorporate distinct biomacromolecules without affecting their intrinsic activity. Herein, a metal-phenolic assembly approach is presented whereby diverse functional nanoparticles can be readily assembled in water by combining various synthetic and natural building blocks, including poly(ethylene glycol), phenolic ligands, metal ions, and bioactive macromolecules. The assembly process is primarily mediated by metal-phenolic complexes through coordination and hydrophobic interactions, which yields uniform and spherical nanoparticles (mostly <200 nm), while preserving the function of the incorporated biomacromolecules (siRNA and five different proteins used). The functionality of the assembled nanoparticles is demonstrated through cancer cell apoptosis, RNA degradation, catalysis, and gene downregulation studies. Furthermore, the resulting nanoparticles can be used as building blocks for the secondary engineering of superstructures via templating and cross-linking with metal ions. The bioactivity and versatility of the platform can potentially be used for the streamlined and rational design of future bioactive materials.

Supramolecular assembly affords the development of a wide range of polypeptide-based biomaterials for drug delivery and nanomedicine. However, there remains a need to develop a platform for the rapid synthesis and study of diverse polypeptide-based materials without the need for employing complex chemistries. Herein, we develop a versatile strategy for creating polypeptide-based materials using polyphenols that display multiple synergistic cross-linking interactions with different polypeptide side groups. We evaluated the diverse interactions operating within these polypeptide-polyphenol networks via binding affinity, thermodynamics, and molecular docking studies and found that positively charged polypeptides (Ka of ∼2 × 104 M-1) and polyproline (Ka of ∼2 × 106 M-1) exhibited stronger interactions with polyphenols than other amino acids (Ka of ∼2 × 103 M-1). Free-standing particles (capsules) were obtained from different homopolypeptides using a template-mediated strategy. The properties of the capsules varied with the homopolypeptide used, for example, positively charged polypeptides produced thicker shell walls (120 nm) with reduced permeability and involved multiple interactions (i.e., electrostatic and hydrogen), whereas uncharged polypeptides generated thinner (10 nm) and more permeable shell walls due to the dominant hydrophobic interactions. Polyarginine imparted cell penetration and endosomal escape properties to the polyarginine-tannic acid capsules, enabling enhanced delivery of the drug doxorubicin (2.5 times higher intracellular fluorescence after 24 h) and a corresponding higher cell death in vitro when compared with polyproline-tannic acid capsules. The ability to readily complex polyphenols with different types of polypeptides highlights that a wide range of functional materials can be generated for various applications.

Coordination states of metal-organic materials are known to dictate their physicochemical properties and applications in various fields. However, understanding and controlling coordination sites in metal-organic systems is challenging. Herein, we report the synthesis of site-selective coordinated metal-phenolic networks (MPNs) using flavonoids as coordination modulators. The site-selective coordination was systematically investigated experimentally and computationally using ligands with one, two, and multiple different coordination sites. Tuning the multimodal Fe coordination with catechol, carbonyl, and hydroxyl groups within the MPNs enabled the facile engineering of diverse physicochemical properties including size, selective permeability (20-2000 kDa), and pH-dependent degradability. This study expands our understanding of metal-phenolic chemistry and provides new routes for the rational design of structurally tailorable coordination-based materials.

Soft structures in nature, such as supercoiled DNA and proteins, can organize into complex hierarchical architectures through multiple noncovalent molecular interactions. Identifying new classes of natural building blocks capable of facilitating long-range hierarchical structuring has remained an elusive goal. We report the bottom-up synthesis of a hierarchical metal-phenolic mesocrystal where self-assembly proceeds on different length scales in a spatiotemporally controlled manner. Phenolic-based coordination complexes organize into supramolecular threads that assemble into tertiary nanoscale filaments, lastly packing into quaternary mesocrystals. The hierarchically ordered structures are preserved after thermal conversion into a metal-carbon hybrid framework and can impart outstanding performance to sodium ion batteries, which affords a capability of 72.5 milliampere hours per gram at an ultrahigh rate of 200 amperes per gram and a 90% capacity retention over 15,000 cycles at a current density of 5.0 amperes per gram. This hierarchical structuring of natural polyphenols is expected to find widespread applications.

Supramolecular complexation is a powerful strategy for engineering materials in bulk and at interfaces. Metal–phenolic networks (MPNs), which are assembled through supramolecular complexes, have emerged as suitable candidates for surface and particle engineering owing to their diverse properties. Herein, we examine the supramolecular dynamics of MPNs during thermal transformation processes. Changes in the local supramolecular network including enlarged pores, ordered aromatic packing, and metal relocation arise from thermal treatment in air or an inert atmosphere, enabling the engineering of metal–oxide networks (MONs) and metal–carbon networks, respectively. Furthermore, by integrating photo‐responsive motifs (i.e., TiO2) and silanization, the MONs are endowed with reversible superhydrophobic (>150°) and superhydrophilic (≈0°) properties. By highlighting the thermodynamics of MPNs and their transformation into diverse materials, this work offers a versatile pathway for advanced materials engineering.

X-ray-based analytics are routinely applied in many fields, including physics, chemistry, materials science, and engineering. The full potential of such techniques in the life sciences and medicine, however, has not yet been fully exploited. We highlight current and upcoming advances in this direction. We describe different X-ray-based methodologies (including those performed at synchrotron light sources and X-ray free-electron lasers) and their potentials for application to investigate the nano-bio interface. The discussion is predominantly guided by asking how such methods could better help to understand and to improve nanoparticle-based drug delivery, though the concepts also apply to nano-bio interactions in general. We discuss current limitations and how they might be overcome, particularly for future use in vivo.

Poly(ethylene glycol) (PEG) is well known to endow nanoparticles (NPs) with low-fouling and stealth-like properties that can reduce immune system clearance in vivo, making PEG-based NPs (particularly sub-100 nm) of interest for diverse biomedical applications. However, the preparation of sub-100 nm PEG NPs with controllable size and morphology is challenging. Herein, we report a strategy based on the noncovalent coordination between PEG-polyphenolic ligands (PEG-gallol) and transition metal ions using a water-in-oil microemulsion phase to synthesize sub-100 nm PEG NPs with tunable size and morphology. The metal-phenolic coordination drives the self-assembly of the PEG-gallol/metal NPs: complexation between MnII and PEG-gallol within the microemulsions yields a series of metal-stabilized PEG NPs, including 30-50 nm solid and hollow NPs, depending on the MnII/gallol feed ratio. Variations in size and morphology are attributed to the changes in hydrophobicity of the PEG-gallol/MnII complexes at varying MnII/gallol ratios based on contact angle measurements. Small-angle X-ray scattering analysis, which is used to monitor the particle size and intermolecular interactions during NP evolution, reveals that ionic interactions are the dominant driving force in the formation of the PEG-gallol/MnII NPs. pH and cytotoxicity studies, and the low-fouling properties of the PEG-gallol/MnII NPs confirm their high biocompatibility and functionality, suggesting that PEG polyphenol-metal NPs are promising systems for biomedical applications.

Engineering coatings with precise physicochemical properties allows for control over the interface of a material and its interactions with the surrounding environment. However, assembling coatings with well-defined properties on different material classes remains a challenge. Herein, we report a co-assembly strategy to precisely control the structure and properties (e.g., thickness, adhesion, wettability, and zeta potential) of coatings on various materials (27 substrates examined) using quinone and polyamine building blocks. By increasing the length of the amine building blocks from small molecule diamines to branched amine polymers, we tune the properties of the films, including the thickness (from ca. 5 to ca. 50 nm), interfacial adhesion (0.05 to 5.54 nN), water contact angle (130 to 40°), and zeta potential (-42 to 28 mV). The films can be post-functionalized through the in situ formation of diverse nanostructures, including nanoparticles, nanorods, and nanocrystals. Our approach provides a platform for the rational design of engineered, substrate-independent coatings for various applications.

STUDY QUESTION: Can vascular endothelial growth factor (VEGF)-loaded silica supraparticles (V-SPs) be used as a novel mode of delivering VEGF to the developing preimplantation embryo in vitro? SUMMARY ANSWER: Supplementation of embryo culture media with V-SPs promoted embryonic development in a manner equivalent to media supplemented with free VEGF. WHAT IS KNOWN ALREADY: VEGF is a maternally derived growth factor that promotes preimplantation embryonic development in vitro. However, its use in clinical media has limitations due to its low stability in solution. STUDY DESIGN, SIZE, DURATION: This study was a laboratory-based analysis utilising a mouse model. V-SPs were prepared in vitro and supplemented to embryonic culture media. The bioactivity of V-SPs was determined by analysis of blastocyst developmental outcomes (blastocyst development rate and total cell number). PARTICIPANTS/MATERIALS, SETTING, METHODS: SPs were loaded with fluorescently labelled VEGF and release kinetics were characterised. Bioactivity of unlabelled VEGF released from V-SPs was determined by analysis of embryo developmental outcomes (blastocyst developmental rate and total cell number) following individual mouse embryo culture in 20 µl of G1/G2 media at 5% oxygen, supplemented with 10 ng/ml recombinant mouse VEGF in solution or with V-SPs. The bioactivity of freeze-dried V-SPs was also assessed to determine the efficacy of cryostorage. MAIN RESULTS AND THE ROLE OF CHANCE: VEGF release kinetics were characterised by an initial burst of VEGF from loaded spheres followed by a consistent lower level of VEGF release over 48 h. VEGF released from V-SPs resulted in significant increases in total blastocyst cell number relative to the control (P < 0.001), replicating the effects of medium freely supplemented with fresh VEGF (P < 0.001). Similarly, freeze dried V-SPs exerted comparable effects on embryonic development (P < 0.05). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In this proof

The buffering effects displayed by pH‐responsive polymers have recently gained attention in diverse fields such as nanomedicine and water treatment. However, creating libraries of modular and versatile polymers that can be readily integrated within existing materials remains challenging, hence restricting applications inspired by their buffering capacity. Herein, we propose the use of metal–phenolic networks (MPNs) as tunable buffering systems and through mechanistic studies show that their buffering effects are driven by pH‐responsive, multivalent metal–phenolic coordination. Owing to such supramolecular interactions, MPNs exhibit ~2‐fold and 3‐fold higher buffering capacity than polyelectrolyte complexes and commercial buffer solutions, respectively. We demonstrate that the MPN buffering effects are retained after deposition onto solid supports, thereby allowing stabilization of aqueous environmental pH for 1 week. Moreover, by using different metals and ligands for the films, the endosomal escape capabilities of coated nanoparticles can be tuned, where higher buffering capacity leads to greater endosomal escape. This study forms a fundamental basis for developing future metal–organic buffering materials.

Engineering coatings with precise physicochemical properties allows for control over the interface of a material and its interactions with the surrounding environment. However, assembling coatings with well‐defined properties on different material classes remains a challenge. Herein, we report a co‐assembly strategy to precisely control the structure and properties (e.g., thickness, adhesion, wettability, and zeta potential) of coatings on various materials (27 substrates examined) using quinone and polyamine building blocks. By increasing the length of the amine building blocks from small molecule diamines to branched amine polymers, we tune the properties of the films, including the thickness (from ca. 5 to ca. 50 nm), interfacial adhesion (0.05 to 5.54 nN), water contact angle (130 to 40°), and zeta potential (−42 to 28 mV). The films can be post‐functionalized through the in situ formation of diverse nanostructures, including nanoparticles, nanorods, and nanocrystals. Our approach provides a platform for the rational design of engineered, substrate‐independent coatings for various applications.

Surface chemistry is a major factor that determines the wettability of materials, and devising broadly applicable coating strategies that afford tunable and selective surface properties required for next-generation materials remains a challenge. Herein, we report fluorinated metal-organic coatings that display water-wetting and oil-repelling characteristics, a wetting phenomenon different from responsive wetting induced by external stimuli. We demonstrate this selective wettability with a library of metal-organic coatings using catechol-based coordination and silanization (both fluorinated and fluorine-free), enabling sensing through interfacial reconfigurations in both gaseous and liquid environments, and establish a correlation between the coating wettability and polarity of the liquids. This selective wetting performance is substrate-independent, spontaneous, durable, and reversible and occurs over a range of polar and nonpolar liquids (60 studied). These results provide insight into advanced liquid-solid interactions and a pathway toward tuning interfacial affinities and realizing robust, selective superwettability according to the surrounding conditions.

Nanobiohybrids, synthesized by integrating functional nanomaterials with living systems, have emerged as an exciting branch of research at the interface of materials engineering and biological science. Nanobiohybrids use synthetic nanomaterials to impart organisms with emergent properties outside their scope of evolution. Consequently, they endow new or augmented properties that are either innate or exogenous, such as enhanced tolerance against stress, programmed metabolism and proliferation, artificial photosynthesis, or conductivity. Advances in new materials design and processing technologies made it possible to tailor the physicochemical properties of the nanomaterials coupled with the biological systems. To date, many different types of nanomaterials have been integrated with various biological systems from simple biomolecules to complex multicellular organisms. Here, we provide a critical overview of recent developments of nanobiohybrids that enable new or augmented biological functions that show promise in high-tech applications across many disciplines, including energy harvesting, biocatalysis, biosensing, medicine, and robotics.

Functional coatings are of considerable interest because of their fundamental implications for interfacial assembly and promise for numerous applications. Universally adherent materials have recently emerged as versatile functional coatings; however, such coatings are generally limited to catechol, (ortho‐diphenol)‐containing molecules, as building blocks. Here, we report a facile, biofriendly enzyme‐mediated strategy for assembling a wide range of molecules (e.g., 14 representative molecules in this study) that do not natively have catechol moieties, including small molecules, peptides, and proteins, on various surfaces, while preserving the molecule's inherent function, such as catalysis (≈80 % retention of enzymatic activity for trypsin). Assembly is achieved by in situ conversion of monophenols into catechols via tyrosinase, where films form on surfaces via covalent and coordination cross‐linking. The resulting coatings are robust, functional (e.g., in protective coatings, biological imaging, and enzymatic catalysis), and versatile for diverse secondary surface‐confined reactions (e.g., biomineralization, metal ion chelation, and N‐hydroxysuccinimide conjugation).

Nanomedicine as a research field has existed for about two decades, and it is therefore timely to discuss what the next 20 years in nanomedicine should accomplish to provide a scientifically grounded framework for sustained success. To further advance nanomedicine, emphasis should be on integration of hypothesis-driven research principles of medicine with the industrially relevant design principles of nanomaterials. The recently emerging but significantly successful field of immuno-oncology serves as an example of how fundamental research leads to translational success: mechanisms of action are first determined, followed by target molecule identification, and finally in vivo testing with appropriately designed and controlled studies.(1) From the materials science perspective, the rapid development of photovoltaics demonstrates how reproducibility is important to allow for field-wide objective comparisons to be made prior to industrial adoption.(2) The nanomedicine field could also benefit from delineating more clearly whether a study is addressing fundamental or translational questions.(3) Both should be encouraged, but focused, rigorous, and reproducible study designs are essential to facilitate scientific advances as well as comparative studies aimed at commercial outcomes.

Developing materials with programmable permeability for cargo encapsulation and release is challenging but important in a number of fields including drug delivery and sensing. Metal–phenolic networks (MPNs) are an emerging class of hybrid coordination materials with pH-responsiveness and modularity that can be engineered into functional thin films for diverse applications. Herein, we engineer MPN-based microcapsules with a dynamic gating mechanism by adjusting the intermolecular interactions in the capsules. Altering the choice of building blocks and precursor ratio provides an intrinsic and modular means of tailoring capsule size and permeability. Alternatively, regulating the pH of the environment, and thereby the protonation states of MPNs, extrinsically enables capsules to switch between highly permeable (>90% of capsules permeable at pH 9) and near-impermeable (<20% at pH 3) states. These findings provide insights into the dynamic nature of MPNs and offer a route to engineer smart delivery systems and selective gating materials.

Functional materials composed of proteins have attracted much interest owing to the inherent and diverse functionality of proteins. However, establishing general techniques for assembling proteins into nanomaterials is challenging owing to the complex physicochemical nature and potential denaturation of proteins. Here, a simple, versatile strategy is introduced to fabricate functional protein assemblies through the interfacial assembly of proteins and polyphenols (e.g., tannic acid) on various substrates (organic, inorganic, and biological). The dominant interactions (hydrogen-bonding, hydrophobic, and ionic) between the proteins and tannic acid were elucidated; most proteins undergo multiple noncovalent stabilizing interactions with polyphenols, which can be used to engineer responsiveness into the assemblies. The proteins retain their structure and function within the assemblies, thereby enabling their use in various applications (e.g., catalysis, fluorescence imaging, and cell targeting).

The manipulation of interfacial properties has broad implications for the development of high‐performance coatings. Metal–phenolic networks (MPNs) are an emerging class of responsive, adherent materials. Herein, host–guest chemistry is integrated with MPNs to modulate their surface chemistry and interfacial properties. Macrocyclic cyclodextrins (host) are conjugated to catechol or galloyl groups and subsequently used as components for the assembly of functional MPNs. The assembled cyclodextrin‐based MPNs are highly permeable (even to high molecular weight polymers: 250–500 kDa), yet they specifically and noncovalently interact with various functional guests (including small molecules, polymers, and carbon nanomaterials), allowing for modular and reversible control over interfacial properties. Specifically, by using either hydrophobic or hydrophilic guest molecules, the wettability of the MPNs can be readily tuned between superrepellency (>150°) and superwetting (ca. 0°).

The orientation-specific immobilization of antibodies onto nanoparticles, to preserve antibody-antigen recognition, is a key challenge in developing targeted nanomedicines. Herein, we report the targeting ability of metal-phenolic network (MPN)-coated gold nanoparticles with surface-physisorbed antibodies against respective antigens. The MPN coatings were self-assembled from metal ions (FeIII, CoII, CuII, NiII, or ZnII) cross-linked with tannic acid. Upon physisorption of antibodies, all particle systems exhibited enhanced association with target antigens, with CoII systems demonstrating more than 2-fold greater association. These systems contained more metal atoms distributed in a way to specifically interact with antibodies, which were investigated by molecular dynamics simulations. A model antibody fragment crystallizable (Fc) region in solution with CoII-tannic acid complexes revealed that the solvent-exposed CoII can directly coordinate to the histidine-rich portion of the Fc region. This one-pot interaction suggests anchoring of the antibody Fc region to the MPN on nanoparticles, allowing for enhanced targeting.

Adhesion occurs by covalent bonding, as in reactive structural adhesives, or through noncovalent interactions, which are nearly ubiquitous in nature. A classic example of the latter is gecko feet, where hierarchical features enhance friction across the contact area. Biomimicry of such structured adhesion is regularly achieved by top‐down lithography, which allows for direction‐dependent detachment. However, bottom‐up approaches remain elusive given the scarcity of building blocks that yield strong, cohesive, self‐assembly across multiple length scales. Herein, an exception is introduced, namely, aqueous dispersions of cellulose nanocrystals (CNCs) that form superstructured, adherent layers between solid surfaces upon confined evaporation‐induced self‐assembly (C‐EISA). The inherently strong CNCs (EA > 140 GPa) align into rigid, nematically ordered lamellae across multiple length scales as a result of the stresses associated with confined evaporation. This long‐range order produces remarkable anisotropic adhesive strength when comparing in‐plane (≈7 MPa) and out‐of‐plane (≤0.08 MPa) directions. These adhesive attributes, resulting from self‐assembly, substantially outperform previous biomimetic adhesives obtained by top‐down microfabrication (dry adhesives, friction driven), and represent a unique fluid (aqueous)‐based system with significant anisotropy of adhesion. By using C‐EISA, new emergent properties will be closely tied with the nature of colloids and their hierarchical assemblies.

Functional coatings are of considerable interest because of their fundamental implications for interfacial assembly and promise for numerous applications. Universally adherent materials have recently emerged as versatile functional coatings; however, such coatings are generally limited to catechol, (ortho‐diphenol)‐containing molecules, as building blocks. Here, we report a facile, biofriendly enzyme‐mediated strategy for assembling a wide range of molecules (e.g., 14 representative molecules in this study) that do not natively have catechol moieties, including small molecules, peptides, and proteins, on various surfaces, while preserving the molecule's inherent function, such as catalysis (≈80 % retention of enzymatic activity for trypsin). Assembly is achieved by in situ conversion of monophenols into catechols via tyrosinase, where films form on surfaces via covalent and coordination cross‐linking. The resulting coatings are robust, functional (e.g., in protective coatings, biological imaging, and enzymatic catalysis), and versatile for diverse secondary surface‐confined reactions (e.g., biomineralization, metal ion chelation, and N‐hydroxysuccinimide conjugation).

Mesoporous metal-organic networks have attracted widespread interest owing to their potential applications in diverse fields including gas storage, separations, catalysis, and drug delivery. Despite recent advances, the synthesis of metal-organic networks with large and ordered mesochannels (>20 nm), which are important for loading, separating, and releasing macromolecules, remains a challenge. Herein, we report a templating strategy using sacrificial double cubic network polymer cubosomes (Im3̅m) to synthesize ordered mesoporous metal-phenolic particles (meso-MPN particles) with a large-pore (∼40 nm) single cubic network (Pm3̅m). We demonstrate that the large-pore network and the phenolic groups in the meso-MPN particles enable high loadings of various proteins (e.g., horseradish peroxidase (HRP), bovine hemoglobin, immunoglobulin G, and glucose oxidase (GOx)), which have different shapes, charges, and sizes (i.e., molecular weights spanning 44-160 kDa). For example, GOx loading in the meso-MPN particles was 362 mg g-1, which is ∼6-fold higher than the amount loaded in commercially available SiO2 particles with an average pore size of 50 nm. Furthermore, we show that HRP, when loaded in the meso-MPN particles (486 mg g-1), retained ∼82% activity of free HRP in solution and can be recycled at least five times with a minimal (∼13%) decrease in HRP activity, which exceeds HRP performance in 50 nm pore SiO2 particles (∼36% retained activity and ∼30% activity loss when recycled five times). Considering the wide selection of naturally abundant polyphenols (>8000 species) and metal ions available, the present cubosome-enabled strategy is expected to provide new avenues for designing a range of meso-MPN particles for various applications.

The adsorption of biomolecules onto nanomaterials can alter the performance of the nanomaterials in vitro and in vivo. Recent studies have primarily focused on the protein “corona”, formed upon adsorption of proteins onto nanoparticles in biological fluids, which can change the biological fate of the nanoparticles. Conversely, interactions between nanomaterials and other classes of biomolecules namely, lipids, nucleic acids, and polysaccharides have received less attention despite their important roles in biology. A possible reason is the challenge associated with investigating biomolecule interactions with nanomaterials using current technologies. Herein, a protocol is developed for studying bio–nano interactions by depositing four classes of biomolecules (proteins, lipids, nucleic acids, and polysaccharides) and complex biological media (blood) onto planar substrates, followed by exposure to metal–phenolic network (MPN) complexes. The MPNs preferentially interact with the biomolecule over the inorganic substrate (glass), highlighting that patterned biomolecules can be used to engineer patterned MPNs. Subsequent formation of silver nanoparticles on the MPN films maintains the patterns and endows the films with unique reflectance and fluorescence properties, enabling visualization of latent fingerprints (i.e., invisible residual biomolecule patterns). This study demonstrates the potential complexity of the biomolecule corona as all classes of biomolecules can adsorb onto MPN-based nanomaterials.

Synthetic nano/micromotors are a burgeoning class of materials with vast promise for applications ranging from environmental remediation to nanomedicine. The motility of these motors is generally controlled by the concentration of accessible fuel, and therefore, engineering speed-regulation mechanisms, particularly using biological triggers, remains a continuing challenge. Here, control over the movement of superassembled porous framework micromotors via a reversible, biological-relevant pH-responsive regulatory mechanism is demonstrated. Succinylated β-lactoglobulin and catalase are superassembled in porous framework particles, where the β-lactoglobulin is permeable at neutral pH. This permeability allows the fuel (H 2 O 2 ) to access catalase, leading to autonomous movement of the micromotors. However, at mild acidic pH, succinylated β-lactoglobulin undergoes a reversible gelation process, preventing the access of fuel into the micromotors where the catalase resides. To one's knowledge, this study represents the first example of chemically driven motors with rapid, reversible pH-responsive motility. Furthermore, the porous framework significantly enhances the biocatalytic activity of catalase, allowing ultralow H 2 O 2 concentrations to be exploited at physiological conditions. It is envisioned that the simultaneous exploitation of pH and chemical potential of such nanosystems could have potential applications as stimulus-responsive drug delivery vehicles that benefit from the complex biological environment.

Zeolitic imidazolate frameworks (ZIFs) have been widely investigated for their use in separation, gas adsorption, catalysis, and biotechnology. Their practical applications, however, can be hampered by their structural instability in humid acidic conditions. Here, guided by density functional theory calculations, we demonstrate that the acidic stability of two polymorphic ZIFs (i.e., ZIF-8 and ZIF-L) can be enhanced by the incorporation of functional groups on polypeptides or DNA. A range of complementary synchrotron investigations into the local chemical structure and bonding environment suggest that the enhanced acidic stability arises from the newly established coordinative interactions between the Zn centers and the inserted carboxylate (for polypeptides) or phosphate (for DNA) groups, both of which have lower pKas than the imidazolate ligand. With functional biomolecular homologs (i.e., enzymes), we demonstrate a symbiotic stability reinforcement effect, i.e., the encapsulated biomolecules stabilize the ZIF matrix while the ZIF exoskeleton protects the enzyme from denaturation. Metal-organic frameworks (MOFs) have been regarded as promising candidates in environmental remediation situations, energy harvesting, and bio-applications. The facile in situ formation of crystalline zeolitic imidazolate frameworks (ZIFs) in particular allows the encapsulation of sensitive bioentities such as polypeptides, DNA, antibodies, exosomes, enzymes, and even living cells. This enables their use in a wide range of biomedical applications such as diagnosis, therapy, biocatalysis, and drug delivery. However, the instability of these materials in acidic environments has limited their practical applications thus far. Here, by introducing bioentities with carboxylate or phosphate groups into the original Zn-N coordinative environment, we demonstrate a symbiotic stability reinforcement effect between bioentities and ZIFs. Our findings introduce the principle of regulating the bonding

Drug carriers typically require both stealth and targeting properties to minimize nonspecific interactions with healthy cells and increase specific interaction with diseased cells. Herein, the assembly of targeted poly(ethylene glycol) (PEG) particles functionalized with cyclic peptides containing Arg-Gly-Asp (RGD) (ligand) using a mesoporous silica templating method is reported. The influence of PEG molecular weight, ligand-to-PEG molecule ratio, and particle size on cancer cell targeting to balance stealth and targeting of the engineered PEG particles is investigated. RGD-functionalized PEG particles (PEG-RGD particles) efficiently target U-87 MG cancer cells under static and flow conditions in vitro, whereas PEG and cyclic peptides containing Arg-Asp-Gly (RDG)-functionalized PEG (PEG-RDG) particles display negligible interaction with the same cells. Increasing the ligand-to-PEG molecule ratio improves cell targeting. In addition, the targeted PEG-RGD particles improve cell uptake via receptor-mediated endocytosis, which is desirable for intracellular drug delivery. The PEG-RGD particles show improved tumor targeting (14% ID g-1) when compared with the PEG (3% ID g-1) and PEG-RDG (7% ID g-1) particles in vivo, although the PEG-RGD particles show comparatively higher spleen and liver accumulation. The targeted PEG particles represent a platform for developing particles aimed at balancing nonspecific and specific interactions in biological systems.

The intracellular delivery of functional nanoparticles (NPs) and the release of therapeutic payloads at a target site are central issues for biomedical applications. However, the endosomal entrapment of NPs typically results in the degradation of active cargo, leading to poor therapeutic outcomes. Current advances to promote the endosomal escape of NPs largely involve the use of polycationic polymers and cell-penetrating peptides (CPPs), which both can suffer from potential toxicity and convoluted synthesis/conjugation processes. Herein, we report the use of metal-phenolic networks (MPNs) as versatile and nontoxic coatings to facilitate the escape of NPs from endo/lysosomal compartments. The MPNs, which were engineered from the polyphenol tannic acid and FeIII or AlIII, enabled the endosomal escape of both inorganic (mesoporous silica) and organic (polystyrene and melamine resin) NPs owing to the "proton-sponge effect" arising from the buffering capacity of MPNs. Postfunctionalization of the MPN-coated NPs with low-fouling polymers did not impair the endosomal escape, indicating the modular and generalizable nature of this approach. We envisage that the ease of fabrication, versatility, low cytotoxicity, and promising endosomal escape performance displayed by the MPN coatings offer opportunities for such coatings to be used for the efficient delivery of cytoplasm-targeted therapeutics using NPs.

Phenolic materials have long been known for their use in inks, wood coatings, and leather tanning. However, there has recently been a renewed interest in engineering advanced materials from phenolic building blocks. The intrinsic properties of phenolic compounds, such as metal chelation, hydrogen bonding, pH responsiveness, redox potentials, radical scavenging, polymerization, and light absorbance, have made them a distinct class of structural motifs for the synthesis of functional materials. Materials prepared from phenolic compounds often retain many of these useful properties with synergistic effects in applications ranging from catalysis to biomedicine. This Review provides an overview of the diverse functional materials that can be prepared from natural and synthetic phenolic building blocks, as well as their applications.

Metal-phenolic network (MPN) coatings have generated increasing interest owing to their biologically inspired nature, facile fabrication, and near-universal adherence, especially for biomedical applications. However, a key issue in biomedicine is protein fouling, and the adsorption of proteins on tannic acid-based MPNs remains to be comprehensively studied. Herein, we investigate the interaction of specific biomedically relevant proteins in solution (e.g., bovine serum albumin (BSA), immunoglobulin G (IgG), fibrinogen) and complex biological media (serum) using layer-by-layer-assembled tannic acid/FeIII MPN films. When FeIII was the outermost layer, galloyl-modified poly(2-ethyl-2-oxazoline) (P(EtOx)-Gal) could be grafted to the films through coordination bonds. Protein fouling and bacterial adhesion were greatly suppressed after functionalization with P(EtOx)-Gal and the mass of adsorbed protein was reduced by 79%. Interestingly, larger proteins adsorbed more on both the MPNs and P(EtOx)-functionalized MPNs. This study provides fundamental information on the interactions of MPNs with single proteins, mixtures of proteins as encountered in serum, and the noncovalent, coordination-based, functionalization of MPN films.

Metal-phenolic networks (MPNs) are an emerging class of functional metal-organic materials with a high degree of modularity in terms of the choice of metal ion, phenolic ligand, and assembly method. Although various applications, including drug delivery, imaging, and catalysis, have been studied with MPNs, in the form of films and capsules, the influence of metals and organic building blocks on their mechanical properties is poorly understood. Herein, we demonstrate that the mechanical properties of MPNs can be tuned through choice of the metal ion and/or phenolic ligand. Specifically, the pH of the metal ion solution and/or size of phenolic ligand influence the Young's modulus ( EY) of MPNs (higher pHs and smaller ligands lead to higher EY). This study systematically investigates the roles of both metal ions and ligands on the mechanical properties of metal-organic materials and provides new insight into engineering the mechanical properties of coordination films.

The targeted therapy of metastatic melanoma is an important yet challenging goal that has received only limited attention to date. Herein, green tea polyphenols, (–)‐epigallocatechin‐3‐gallate (EGCG), and lanthanide metal ions (Sm3+) are used as building blocks to engineer self‐assembled SmIII‐EGCG nanocomplexes with synergistically enhanced tumor inhibitory properties. These nanocomplexes have negligible systemic toxic effects on healthy cells but cause a significant reduction in the viability of melanoma cells by efficiently regulating their metabolic pathways. Moreover, the wound‐induced migration of melanoma cells can be efficiently inhibited by SmIII‐EGCG, which is a key criterion for metastatic melanoma therapy. In a mouse melanoma tumor model, SmIII‐EGCG is directly compared with a clinical anticancer drug, 5‐fluorouracil and shows remarkable tumor inhibition. Moreover, the targeted therapy of SmIII‐EGCG is shown to prevent metastatic lung melanoma from spreading to main organs with no adverse side effects on the body weight or organs. These in vivo results demonstrate significant advantages of SmIII‐EGCG over its clinical counterpart. The results suggest that these green tea‐based, self‐assembled nanocomplexes possess all of the key traits of a clinically promising candidate to address the challenges associated with the treatment of advanced stage metastatic melanoma.

Background: Porous micro- and nanoparticles have the capacity to encapsulate a large quantity of therapeutics, making them promising delivery vehicles for a variety of applications. This review aims to highlight the latest development of inorganic and hybrid (inorganic/ organic) particles for drug delivery with an additional emphasis on combatting drug resistant cancer. We go one step further and discuss delivery applications beyond medicinal delivery, as there is generally a translation from medicinal delivery to botanic delivery after a short lag time. Methods: We undertook a search of relevant peer-reviewed publications. The quality of the relevant papers was appraised using standard tools. The characteristics of the papers are described herein, and the relevant material and therapeutic properties are discussed. Results: We discuss 4 classes of porous particles in terms of drug delivery and theranostics. We specifically focus on silica, calcium carbonate, metal-phenolic network, and metalorganic framework particles. Other relevant biomedically relevant applications are discussed and we highlight outstanding therapeutic results in the relevant literature. Conclusion: The findings of this review confirm the importance of studying and utilizing porous particles for therapeutic delivery. Moreover, we show that the properties of porous particles that make them promising for medicinal drug delivery also make them promising candidates for agro-industrial applications.

The quantity of programmed cell death-ligand 1 (PD-L1) is regarded as a predicting factor of clinical response to anti-PD-1 axis immunotherapy. However, the expression of PD-L1 and its prognostic value in hepatocellular carcinoma (HCC) patients remain debated. Meanwhile, the molecular features of PD-1's other ligand, namely PD-L2, as well as its correlation with clinicopathological parameters and HCC tumor microenvironment (TME), are still poorly understood. In this study, immunohistochemistry (IHC) data from 304 HCC patients were used to determine the clinicopathological features of PD-L1 and PD-L2 and their correlation with CD8+ T cells in HCC. Moreover, fresh clinical HCC samples were used to identify the immune cell subtypes expressing PD-L1 and PD-L2. By using The Cancer Genome Atlas (TCGA) dataset, we further assessed the correlation between mutation signature, copy number variation (CNV), number of neoepitopes, immune gene expression, immune/stromal cell infiltration to the expression of PD-L1 and PD-L2. While membrane expression of PD-L2 was observed in 19.1% of tumor samples, no obvious expression of PD-L1 was detected on tumor cell membranes. High expression of PD-L2 on tumor membranes and PD-L1 in immune stroma were both significantly associated with poorer overall survival (OS) and disease-free survival (DFS) outcomes. Flow cytometry analysis and immunofluorescence showed that macrophages were the main immune cell subtype expressing both PD-L1 and PD-L2. Moreover, positive expression of PD-Ls was correlated with higher CD8+ T cells infiltration in immune stroma. CNV analysis showed a similarity between PD-L1 and PD-L2 in affecting gene expression. In addition, higher levels of PD-Ls correlated with higher expression of immune related genes, enhanced cytolytic activity, and larger proportions of immune/stromal cell infiltration. Collectively, our study reveals the impact of both PD-L1 and PD-L2 on the HCC tumor microenvironment for the first time, providi

Article OPEN ACCESS Published: 23 May 2019 Acoustomicrofluidic assembly of oriented and simultaneously activated metal–organic frameworks Heba Ahmed, Amgad R. Rezk, Joseph J. Richardson, Lauren K. Macreadie, Ravichandar Babarao, Edwin L. H. Mayes, Lillian Lee & Leslie Y. Yeo Nature Communicationsvolume 10, Article number: 2282 (2019) | Download Citation Abstract The high surface area and porosity, and limitless compound and network combinations between the metal ions and organic ligands making up metal–organic frameworks (MOFs) offer tremendous opportunities for their use in many applications. While numerous methods have been proposed for the synthesis of MOF powders, it is often difficult to obtain oriented crystals with these techniques. Further, the need for additional post-synthesis steps to activate the crystals and release them from the substrate presents a considerable production challenge. Here, we report an acoustically-driven microcentrifugation platform that facilitates fast convective solutal transport, allowing the synthesis of MOF crystals in as short as five minutes. The crystals are not only oriented due to long-range out-of-plane superlattice ordering aided by molecular dipole polarization under the acoustoelectric coupling, but also simultaneously activated during the synthesis process.

Metal-phenolic networks (MPNs) have received widespread interest owing to their modular incorporation of functional metal ions and phenolic ligands. However, the interaction between MPNs and biomolecules is still relatively unexplored. Herein, we studied the effects of MPN-coated gold nanoparticles on amyloid fibril formation (which is associated with Alzheimer's disease) as a function of the metal ion in the MPN systems. All coated particles examined inhibited amyloid formation, with cobalt(ii) MPN-coated particles exhibiting the highest inhibition activity (90%). Molecular dynamics simulations and quantum mechanics calculations suggested that the geometry of the exposed cobalt coordination site in the cobalt-tannic acid networks facilitates its interactions with histidine and methionine residues in the amyloid beta peptides. Furthermore, the unique structure of cobalt MPNs may enable a wider variety of biomedical applications.