Metal-phenolic Network Research Articles

Tannic acid-inspired star polymers for functional metal-phenolic networks with tunable pore sizes.

Tannic acid (TA) is a structurally undefined natural dendritic polyphenol. Here, we introduce a series of TA-inspired polymers with different arm lengths, Mn, and phenolic groups that can be used to engineer metal-phenolic network (MPN) capsules with different properties including controlled permeability, high biocompatibility, and fluorescence.

Protein precoating modulates biomolecular coronas and nanocapsule-immune cell interactions in human blood.

The biomolecular corona that forms on particles upon contact with blood plays a key role in the fate and utility of nanomedicines. Recent studies have shown that precoating nanoparticles with serum proteins can improve the biocompatibility and stealth properties of nanoparticles. However, it is not fully clear how precoating influences biomolecular corona formation and downstream biological responses. Herein, we systematically examine three precoating strategies by coating bovine serum albumin (single protein), fetal bovine serum (FBS, mixed proteins without immunoglobulins), or bovine serum (mixed proteins) on three nanoparticle systems, namely supramolecular template nanoparticles, metal-phenolic network (MPN)-coated template (core-shell) nanoparticles, and MPN nanocapsules (obtained after template removal). The effect of protein precoating on biomolecular corona compositions and particle-immune cell interactions in human blood was characterized. In the absence of a pre-coating, the MPN nanocapsules displayed lower leukocyte association, which correlated to the lower amount (by 2-3 fold) of adsorbed proteins and substantially fewer immunoglobulins (more than 100 times) in the biomolecular corona relative to the template and core-shell nanoparticles. Among the three coating strategies, FBS precoating demonstrated the most significant reduction in leukocyte association (up to 97% of all three nanoparticles). A correlation analysis highlights that immunoglobulins and apolipoproteins may regulate leukocyte recognition. This study demonstrates the impact of different precoating strategies on nanoparticle-immune cell association and the role of immunoglobulins in bio-nano interactions.

Metal–Phenolic‐Network‐Coated Dendrimer–Drug Conjugates for Tumor MR Imaging and Chemo/Chemodynamic Therapy via Amplification of Endoplasmic Reticulum Stress

AbstractAmplification of endoplasmic reticulum stress (ERS) to realize enhanced cancer therapy has been considered to be unique in current cancer nanomedicine design. Herein, the design of metal–phenolic‐network‐coated dendrimer–drug conjugates as a novel theranostic nanoplatform based on ERS amplification is reported. In the design, acetylated generation‐5 poly(amidoamine) dendrimers are conjugated with an ERS drug, toyocamycin (Toy), through the attached phenylboronic acid moiety, and coated with an iron (Fe)–tannic acid (TF) network. The generated nanocomplexes with a size of 50.2 nm are stable under the physiological environment, and can rapidly release Toy under the tumor microenvironment due to the pH‐ and reactive‐oxygen‐species‐responsive boronic ester bonds to effectively inhibit the ERS‐mediated cancer cell adaptation. Meanwhile, the coated TF network enables the nanocomplexes to generate cytotoxic hydroxyl radicals through a Fenton reaction, amplifying the ERS for improved chemo/chemodynamic therapy of cancer cells in vitro and a xenografted breast tumor model in vivo. Moreover, the coating of TF also renders the complexes with an eminent r1 relaxivity for in vivo T1‐weighted tumor magnetic resonance imaging. The created intelligent nanocomplexes may represent an advanced nanomedicine formulation uniquely integrated with a metal–phenolic network and dendrimer nanotechnology for imaging‐guided cancer therapy through ERS amplification.

Metal Phenolic Nanodressing of Porous Polymer Scaffolds for Enhanced Bone Regeneration via Interfacial Gating Growth Factor Release and Stem Cell Differentiation.

Porous polymer scaffolds are essential materials for tissue engineering because they can be easily processed to deliver stem cells or bioactive factors. However, scaffolds made of synthetic polymers normally lack a bioactive cell-material interface and undergo a burst release of growth factors, which may hinder their further application in tissue engineering. In this paper, a metal-phenolic network (MPN) was interfacially constructed on the pore surface of a porous poly(dl-lactide) (PPLA) scaffold. Based on the molecular gating property of the MPN supramolecular structure, the PPLA@MPN scaffold achieved the sustained release of the loaded molecules. In addition, the MPN coating provided a bioactive interface, thus encouraging the migration and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The PPLA@MPN scaffolds exhibited enhanced bone regeneration in a rat femoral defect model in vivo compared to PPLA, which is ascribed to the combined effect of sustained bone morphogenetic protein-2 (BMP-2) release and the osteogenic ability of MPN. This nanodressing technique provides a viable and straightforward strategy for enhancing the performance of porous polymer scaffolds in bone tissue engineering.

Encapsulation of Chlamydomonas reinhardtii into a metal-phenolic network

Single-cell encapsulation using metal-phenolic networks (MPNs) is an emerging technique to protect cells from stressors. Until now, the MPN coatings have been only applied to some bacteria, yeast, and mammalian cells. To further demonstrate their versatility, we herein coat Chlamydomonas reinhardtii with the network consisting of tannic acid and iron(III). The encapsulation served as a mechanical barrier, which delayed proliferation of the coated cells. Furthermore, we investigated the adsorption of tannic acid onto the surface of C. reinhardtii and identified the optimum concentration to achieve partial coverage on the algae's surface. Finally, we explored the effect of MPN coating for flocculation-enhanced algae harvesting. Overall, the results demonstrate that the cell encapsulation technique using metal-phenolic networks is applicable to the C. reinhardtii, which is promising for the surface engineering of the green algae for energy harvesting and biomedical applications.

Co-delivery of enzymes and photosensitizers via metal-phenolic network capsules for enhanced photodynamic therapy

The intrinsic hypoxic tumor microenvironment and limited accumulation of photosensitizers (PSs) result in unsatisfied efficiency of photodynamic therapy (PDT). To enhance the PDT efficiency against solid tumors, a functional oxygen self-supplying and PS-delivering nanosystem is fabricated via the combination of catalase (CAT), chlorin e6 (Ce6) and metal-phenolic network (MPN) capsule. It is demonstrated that the CAT encapsulated in the capsules (named CCM capsules) could catalyze the degradation of hydrogen peroxide (H2O2) to produce molecular oxygen (O2), which could be converted into cytotoxicity reactive oxygen species (ROS) by surface-loaded Ce6 under 660 nm laser irradiation, leading to synergistic anticancer effects in vitro and in vivo. Therefore, the application of CCM capsule could be a promising strategy to improve PDT effectiveness.

Synthesis of Customizable Macromolecular Conjugates as Building Blocks for Engineering Metal–Phenolic Network Capsules with Tailorable Properties

Metal–phenolic networks (MPNs), formed through coordination bonding between phenolic molecules and metal ions, are a promising class of materials for engineering particle systems for diverse applications. However, the properties of such MPNs are inherently restricted due to the finite properties of naturally occurring phenolic molecules. Herein, we report a simple and robust approach to incorporate phenolic moieties into polymers, thereby providing customizable phenolic ligand building blocks that can be used to assemble capsules with a range of tailorable properties. The phenolic ligand building blocks were synthesized via carbonic anhydride coupling to terminal amines, a conjugation approach typically used for peptide coupling but applied herein for functionalizing polymers. The chemistry enabled optimized end-group purity, thus affording a robust and efficient strategy to generate a library of macromolecular poly(ethylene glycol) (PEG) catechol building blocks with different architectures (i.e., 2-, 4-, and 8-arm) and molecular weights (from 2.5 to 20 kDa). The resulting phenolic building blocks were applied to fabricate capsules with shell thickness, permeability, and cell association properties that were controlled via the variation of the macromolecular catechol architecture and molecular weight. Specifically, the shell thickness was varied more than 19-fold (i.e., between ∼9 and 169 nm) by judicious selection of the polymer molecular weight, arm number, and template. Similarly, the permeability of the resulting MPN capsules to 500 kDa dextran was tuned from >90 to <5% by varying the number of arms in the polymer structure while maintaining a constant PEG Mn-to-catechol group ratio. Furthermore, the cell association was reduced by a factor of 2.5 by employing 20 kDa 8-arm PEG instead of 2.5 kDa 2-arm PEG during film assembly. These results demonstrate that the applied macromolecular conjugation approach can be used to customize particle properties, potentially facilitating applications in therapeutic delivery, imaging, separations, and catalysis.

Versatile metal-phenolic network nanoparticles for multitargeted combination therapy and magnetic resonance tracing in glioblastoma

Glioblastoma multiforme (GBM) is a common malignancy of the central nervous system, but conventional treatments yield unsatisfactory results. Although innovative therapeutic approaches have been developed, they prolong survival by only approximately 5 months. The heterogeneity of GBM renders growth inhibition with a single drug difficult, and exploring combination approaches with multiple targets for the comprehensive treatment of GBM is expected to overcome this limitation. In this study, we designed a biocompatible cRGD/Pt + DOX@GFNPs (RPDGs) nanoformulation to disrupt redox homeostasis in GBM cells and promote the simultaneous occurrence of efficient apoptosis and ferroptosis. Taking advantage of the highly stable Fenton reaction catalytic activity of gallic acid (GA)/Fe2+ nanoparticles in physiological environments, the ability of Pt (IV) to deplete glutathione (GSH) and increase reactive oxygen species (ROS) levels, and the efficient photothermal conversion efficiency of GA/Fe2+ nanoparticles, our synthesized multifunctional and multitargeted RPDGs significantly increased intracellular ROS levels and thus induced ferroptosis. Furthermore, the RPDGs displayed superior photothermal responsiveness and magnetic resonance imaging (MRI) capabilities. These results indicate that RPDGs can not only directly inhibit the growth of tumors but also effectively improve the efficient translocation of conventional chemotherapeutic drugs across the blood-brain barrier, thereby providing a new approach for the comprehensive treatment of GBM.

Encapsulation of Enzymes in Metal-Phenolic Network Capsules for the Trigger of Intracellular Cascade Reactions.

Nanoengineered capsules encapsulated with functional cargos (e.g., enzymes) are of interest for various applications including catalysis, bioreactions, sensing, and drug delivery. Herein, we report a facile strategy to engineer enzyme-encapsulated metal-phenolic network (MPN) capsules using enzyme-loaded zeolitic imidazolate framework nanoparticles (ZIF-8 NPs) as templates, which can be removed in a mild condition (e.g., ethylenediaminetetraacetic acid (EDTA) solution). The capsule size (from 250 nm to 1 μm) and thickness (from 9.8 to 33.7 nm) are well controlled via varying the template size and coating time, respectively. Importantly, MPN capsules encapsulated with enzymes (i.e., glucose oxidase) can trigger the intracellular cascade reaction via the exhaustion of glucose to produce H2O2 and subsequently generate toxic hydroxyl radicals (•OH) based on the Fenton reaction via the reaction between H2O2 and iron ions in MPN coatings. The intracellular cascade reaction for the generation of •OH is efficient to inhibit cancer cell viability, which is promising for the application in chemodynamic therapy.

Electro-Mechanochemical Gating of a Metal-Phenolic Nanocage for Controlled Guest-Release Self-Powered Patches and Injectable Gels.

Recent advances have led to the development of intelligent drug-delivery systems such as microchips, micropumps, and soft devices with sensors; however, the facile preparation of transdermal and implantable systems modulable to various stimuli remains elusive. In addition, the use of a battery limits their wearable and implantable applications. Therefore, to overcome these disadvantages, we herein suggest a facile strategy to prepare electro-mechanochemically responsive soft gel composites with molecular gatekeeper-based nanocontainers. We found that a metal-phenolic coordination network can act as an efficient self-healable and adaptive gatekeeper in response to electrical and mechanical stimuli owing to the reversible dynamic bonds and adhesiveness to the silica surface. The porous channels of mesoporous silica nanoparticles are filled with guest molecules, and the exterior is wrapped with metal-tannic acid (TA) networks. Owing to the robustness of metal-phenolic network, the guest molecules are efficiently entrapped in the channels but released by electrical and ultrasound input. Voltage-dependent changes in the guest release rate provide control over the dosage on demand. The combination of hydrogel matrixes with the responsive nanocapsules enables the construction of a series of adaptive gel composites capable of successive guest release in response to electrical, ultrasound, electromechanical, and triboelectric stimuli. The Korsmeyer-Peppas model revealed that the release mechanism is non-Fickian, which indicates the presence of boundaries around the guest-loading channels (n = 0.739, R2 = 0.9574 when 2 V is applied). This study realized efficient platforms for active-type drug-delivery applications based on transdermal patches and implantable gels with remotely controllable release characteristics.

A step-by-step multiple stimuli-responsive metal-phenolic network prodrug nanoparticles for chemotherapy

A step-by-step multiple stimuli-responsive metal-phenolic network prodrug nanoparticles for chemotherapy

Synthesis of cationic bacterial cellulose using a templated metal phenolic network for antibacterial applications

Synthesis of cationic bacterial cellulose using a templated metal phenolic network for antibacterial applications

Synergistic Anti-inflammatory Coating "Zipped Up" on Polypropylene Hernia Mesh.

Violent inflammation has impeded worry-free application of polypropylene (PP) hernia meshes. Efficient anti-inflammatory coatings are urgently needed to alter the situation. Here, we present a zipper-like, two-layer coating with an intermediate antioxidant layer (I) and an outer antifouling layer (II) to endow PP meshes with synergistic anti-inflammatory effects. The controllable antioxidant ability of layer I was obtained by modulating the assembly cycle of the metal-phenolic network (MPN) composed of tannic acid (TA) and Fe3+. Polyzwitterionic (PMAD) brush-based layer II was generated upon multiple interactions between the catechol side groups of PMAD and layer I. To consolidate the entire assembly architecture, aryloxy radical coupling was initiated through alkali-catalyzed oxidation. The reaction is similar to a "zipping up" process to construct covalent bonds in the I-II interface and layer I by coupling adjacent catechol groups, which facilely achieved grafting and cross-linking. The obtained coating (PMAD-TA/Fe) did not affect the original properties of the PP mesh and remained stable during cyclic tensile testing or degradation. Most importantly, the excellent antioxidant and antifouling capacities enabled PMAD-TA/Fe-PP to exhibit desirable anti-inflammatory effects and reduce collagen deposition when compared with the bare material. The synergistic anti-inflammatory coating eliminates a major hindrance in the design of biocompatible meshes, and its potential application in developing medical implants with low immunogenicity is promising.

Quantitatively Tracking Bio-Nano Interactions of Metal-Phenolic Nanocapsules by Mass Cytometry.

Polymer nanocapsules, with a hollow structure, are increasingly finding widespread use as drug delivery carriers; however, quantitatively evaluating the bio-nano interactions of nanocapsules remains challenging. Herein, poly(ethylene glycol) (PEG)-based metal-phenolic network (MPN) nanocapsules of three sizes (50, 100, and 150 nm) are engineered via supramolecular template-assisted assembly and the effect of the nanocapsule size on bio-nano interactions is investigated using in vitro cell experiments, ex vivo whole blood assays, and in vivo rat models. To track the nanocapsules by mass cytometry, a preformed gold nanoparticle (14 nm) is encapsulated into each PEG-MPN nanocapsule. The results reveal that decreasing the size of the PEG-MPN nanocapsules from 150 to 50 nm leads to reduced association (up to 70%) with phagocytic blood cells in human blood and prolongs in vivo systemic exposure in rat models. The findings provide insights into MPN-based nanocapsules and represent a platform for studying bio-nano interactions.

One-step synthesis of nitrogen-grafted copper-gallic acid for enhanced methylene blue removal

Nitrogen-grafting through the addition of glycine (Gly) was performed on a metal- phenolic network (MPN) of copper (Cu2+) and gallic acid (GA) to increase its adsorption capacity. Herein, we reported a one-step synthesis method of MPN, which was developed according to the metal–ligand complexation principle. The nitrogen grafted CuGA (Ng-CuGA) MPN was obtained by reacting Cu2+, GA, and Gly in an aqueous solution at a molar ratio of 1:1:1 and a pH of 8. Several physicochemical measurements, such as Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), N2 sorption, X-ray diffraction (XRD), and thermal gravimetry analysis (TGA), were done on Ng-CuGA to elucidate its characteristics. The analysis revealed that the Ng-CuGA has non-uniform spherical shaped morphology with a pore volume of 0.56 cc/g, a pore size of 23.25 nm, and thermal stability up to 205 °C. The applicational potential of the Ng-CuGA was determined based on its adsorption capacity against methylene blue (MB). The Ng-CuGA was able to adsorb 190.81 mg MB per g adsorbent at a pH of 6 and temperature of 30 °C, which is 1.53 times higher than the non-grafted CuGA. Detailed assessment of Ng-CuGA adsorption properties revealed their pH- and temperature-dependent nature. The adsorption capacity and affinity were found to decrease at a higher temperature, demonstrating the exothermic adsorption behavior.

In Situ Growth Large Area Silver Nanostructure on Metal Phenolic Network Coated NAAO Film and Its SERS Sensing Application for Monofluoroacetic Acid.

Rapid screening monofluoroacetic acid (FAcOH) is responsible for preventing chemical poisoning and food safety events. Whereas surface enhanced Raman scattering (SERS) spectra is an effective tool for detecting forbidden chemicals, it is difficult to directly detect FAcOH due to its small Raman scattering cross section as well as weak adsorption on SERS substrates. In this work, the metal phenolic supramolecular networks (MPNs, i.e., the tannic acid and Fe3+ complex) were fabricated on the commercial nanoanodic aluminum oxide film (NAAO) for assisting in situ chemical deposition highly uniform Ag nanostructure over large areas (the NAAO@AgNS). The low cost and simple fabrication process made the NAAO@AgNS a single-use consumable. For FAcOH detection, a specific derivative reaction between FAcOH and thiosalicylic acid (TSA) was introduced. By taking TSA as the Raman probe, its SERS signal attenuated constantly with the increasing amount of FAcOH. For improving quantitative accuracy, thiocyanate (SCN-) was introduced on the NAAO@AgNS as an internal standard; thus, the characteristic peak intensity ratios associated with TSA and SCN- (I1035/I2125) were fitted to the concentration of FAcOH. It was demonstrated that the SERS assay achieved good sensitivity and selection toward FAcOH with the limit of quantitation (LOD) as low as 50 nmol L-1. The NAAO@AgNS featured with highly sensitive, uniform, and consistent SERS performances could easily extend to wide SERS applications.

Safeguarding Osteointegration in Diabetic Patients: A Potent “Chain Armor” Coating for Scavenging ROS and Macrophage Reprogramming in a Microenvironment‐Responsive Manner

AbstractRisk of implant failure increases profoundly in patients with pre‐existing conditions (e.g., diabetes). Current therapies adopt a one‐sided focus on the direct antibacterial properties of biomaterials and osteogenesis stimulation. However, in this study it is demonstrated that a “chain armor” structure (Ce‐TA) that mainly targets the regulation of the local pathological microenvironment, provides a novel solution to scavenge reactive oxygen species (ROS) by simulating superoxide dismutase and catalase and significantly improving osteointegration under diabetic conditions. Ce‐TA based on a metal phenolic network biological functional interface is successfully constructed. Ce‐TA, an ultrathin armor structure, is biocompatible and facile. Through in vitro assays it is demonstrated that Ce‐TA reshapes the diabetic microenvironment into a regenerative one in a microenvironment‐responsive manner, where Ce‐TA regulates hypoxia‐inducible factor 1α (HIF‐1α) activity by reducing the level of mitochondrial ROS, and effectively alleviates mitochondrial dysfunction and reprogrammes macrophages to a pro‐healing state. Furthermore, it is confirmed that Ce‐TA shows excellent therapeutic effects on the reducing postoperative infection and enhances osteointegration of intra‐osseous implants in diabetic rat models. The proposed strategy opens up a promising opportunity for repurposing metals with intrinsic enzyme‐like activity for the goal of enhancing the osteointegration of devices with orthopedic and dental applications among diabetic patients.

Facile fabrication of superhydrophilic and underwater superoleophobic nanofiber membranes for highly efficient separation of oil-in-water emulsion

• Superhydrohilic/underwater superoleophobic ENMs is prepared by MPNs coating technique. • The influence TA/Fe concentrations and number of coating cycles in MPN were studied. • The ENMs were used to separate O/W mixture and emulsion in dead-end and cross-flow systems. • The ENMs showed an outstanding performance under ultra-low transmembrane pressure. • The ENMs exhibits a remarkable recovery ability and excellent oil rejection. Electrospun nanofiber membrane (ENM)-based filtration is an advanced technology that treats wastewater for reuse using gravity or low pressure as a driving force, thereby solving water scarcity in a way that is suitable for conditions of energy scarcity. The high hydrophobicity of ENMs remains the main challenge for their application in the treatment of oily wastewater. Although some techniques have succeeded in enhancing surface wettability, their disadvantages (e.g., difficulty, harsh operating conditions, harmful environmental effects, time consumption, or high costs) restrict the scalability and industrial application of those techniques. Herein, superhydrohilic and underwater superoleophobic ENMs were prepared using a two-step metal-phenolic network (MPN) coating process as a scalable, cost-effective, green, and powerful technique. The fabricated nanocoated-ENMs showed superhydrophilicity at air and even underoil, as well as underwater superoleophobicity. Thus, they could separate the oil-in-water mixture and surfactant-stabilized oil-in-water emulsion with outstanding flux values of 6.5 × 10 4 and >6.0 × 10 3 L/m 2 .h, respectively, and a remarkable recovery ability (up to 99.8%) and excellent oil rejection (up to 99.9%), using only gravity as a driving force. More importantly, the nanocoated-ENMs showed a stable and ultrahigh flux up to 13,756.7 L/m 2 .h, with a separation efficiency of 97.5%, for surfactant-stabilized oil-in-water emulsion in a continuous cross-flow separation system, at an ultralow transmembrane pressure of 5 kPa. Additionally, the nanocoated-ENMs exhibited excellent chemical stability, durability, and robust reusability under harsh environments. Interestingly, the obtained fluxes are more superior to most reported values, at the same conditions, and higher than that of the commercial membranes with one to two orders of magnitude, pointing to the significant applicability for energy-saving large-scale oily wastewater treatment process.

Metal-phenolic network-coated hollow fiber catalytic membranes via solvent transfer induced phase separation (STRIPS) for Suzuki coupling reaction

Catalytically reactive membranes enable continuous and high yield chemical reactions while obviating the need for catalyst separation from the product stream. Despite recent advances, there still exists considerable challenges in developing high performance catalytic membranes. Most works to date have used planar membranes made of chemically inert materials, limiting conversion efficiency due to their low specific surface area and difficulty associated with incorporating a high density of catalytic nanoparticles on their surface. To overcome these limitations, we employ a single-step solvent transfer-induced phase separation (STRIPS) method to prepare nanocomposite hollow fiber membranes. Taking advantage of a dense layer of silica nanoparticles (NPs) on the surface of the STRIPS membrane, catalytic activity is imbued by coating the membrane surface with palladium (Pd)-supported metal-phenolic network (MPN). These catalytic hollow fiber membranes are used to perform Suzuki-Miyaura cross-coupling reactions, enabling continuous production of biaryl compounds with a high conversion efficiency (>90%) while retaining high permeability (>60 L/m2⋅h (LMH) at 1 bar-pressurized condition). The approach presented in this work synergistically combines hollow fiber nanocomposite structures and MPN coating to offer a versatile platform for developing the next generation reactive membranes for synthesizing valuable chemicals.

Phenolic molecules constructed nanomedicine for innovative cancer treatment

• Phenolic molecules are promising building blocks for the construction of functional nanomedicines. • The chemical approaches utilized to construct phenolic nanomedicines are classified and described. • The applications of phenolic nanomedicinies in cancer treatments are discussed according to their action mechanisms. • The perspectives on the construction of phenolic nanomedicines and their potential clinical translation are provided. Construction of innovative nanomedicine with bioderived molecules is of great research interest to achieve effective cancer treatment owing to their intrinsic biocompatibility and biodegradability. By virtue of their intrinsic physiochemical properties, tremendous natural phenolic molecules and their synthetic derivatives have been explored for the construction of diverse functional materials including nanomedicine. In this review, we firstly make a summary on approaches (e.g., oxidative polymerization, metal-phenolic network formation) commonly utilized for the construction of diverse nanomedicine with unique properties by using these phenolic molecules as the building blocks. Later, the applications of these engineered nanomedicine in photothermal therapy, tumor targeted delivery of therapeutic ions, small molecules, and biomacromolecules, as well as tumor microenvironment modulation will be described in detail. Finally, future perspectives on the construction of these phenolic molecules based nanomedicine and their potential clinical translation will be provided.