Metal-phenolic Coordination Research Articles

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.

Oxygen-Enriched Metal-Phenolic X-Ray Nanoprocessor for Cancer Radio-Radiodynamic Therapy in Combination with Checkpoint Blockade Immunotherapy.

Radiotherapy (RT) based on DNA damage and reactive oxygen species (ROS) generation has been clinically validated in various types of cancer. However, high dose‐dependent induced toxicity to tissues, non‐selectivity, and radioresistance greatly limit the application of RT. Herein, an oxygen‐enriched X‐ray nanoprocessor Hb@Hf‐Ce6 nanoparticle is developed for improving the therapeutic effect of RT‐radiodynamic therapy (RDT), enhancing modulation of hypoxia tumor microenvironment (TME) and promoting antitumor immune response in combination with programmed cell death protein 1 (PD‐1) immune checkpoint blockade. All functional molecules are integrated into the nanoparticle based on metal‐phenolic coordination, wherein one high‐Z radiosensitizer (hafnium, Hf) coordinated with chlorin e6 (Ce6) modified polyphenols and a promising oxygen carrier (hemoglobin, Hb) is encapsulated for modulation of oxygen balance in the hypoxia TME. Specifically, under single X‐ray irradiation, radioluminescence excited by Hf can activate photosensitizer Ce6 for ROS generation by RDT. Therefore, this combinatory strategy induces comprehensive antitumor immune response for cancer eradication and metastasis inhibition. This work presents a multifunctional metal‐phenolic nanoplatform for efficient X‐ray mediated RT‐RDT in combination with immunotherapy and may provide a new therapeutic option for cancer treatment.

Phenolic immunogenic cell death nanoinducer for sensitizing tumor to PD-1 checkpoint blockade immunotherapy

A critical challenge remains in PD-1 checkpoint blockade immunotherapy is few tumor specific T cells infiltration in hypoxic tumor microenvironment (TME). Improving immunogenic cell death (ICD) associated immunogenicity can make tumor sensitive to PD-1 checkpoint blockade immunotherapy. Herein, a phenolic ICD inducer was engineered by self-assembly of the superior ICD inducer (doxorubicin, DOX), phenolic manganese dioxide nanoreactor, ferric iron and PEG-polyphenols (MDP NPs) via metal phenolic coordination. These oxygen self-supporting MDP NPs strengthen DOX based ROS-dependent cell death and their metal mediated chemodynamic effect accelerate ICD induction. Together with concomitant ICD triggered by DOX, MDP NPs successively lead to tumor-associated antigen boosting, DCs maturation and ultimately enhance tumor-specific T cells infiltration. Furthermore, MDP NPs efficiently modulated hypoxic TME for effective macrophages recruitment. This promising ICD-augment strategy efficiently improve tumor response to PD-1 checkpoint blockade immunotherapy, resulting in a significant antitumor immune response in primary tumor and a strong abscopal effect to distant tumor. Our simple and versatile phenolic inducer expands the application of chemodrugs based ICD enhancing PD-1 checkpoint blockade immunotherapy.

Microemulsion-Assisted Templating of Metal-Stabilized Poly(ethylene glycol) Nanoparticles.

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.

Preparation of magnetic mesoporous metal-phenolic coordination spheres for extraction of crystal violet and leuco-metabolites in fish

To address the undesirably low porosity of phenolic resin, a new material termed magnetic mesoporous metal-phenolic coordination spheres (Fe3O4@Co-TA) was synthesized by chelating tannic acid (TA) with metal ions. Fe3O4@Co-TA was characterized by transmission electron microscopy, scanning electron microscopy, hysteresis loop (B-H) analysis, Fourier-transform infrared spectroscopy, and N2 adsorption-desorption. The results indicated that the new material comprises mesopores (2 nm and 3 nm) and exhibits a good magnetic response (44 emu/g). Combined with high-performance liquid chromatography (HPLC), a novel method for the detection of crystal violet (CV) and leucocrystal violet (LCV) by magnetic solid-phase extraction was established. Under the optimal extraction conditions, the linear ranges of CV and LCV detection were 0.2‒60 μg/L and 0.04‒40 μg/L, the detection limits were 0.04 μg/L and 0.008 μg/L, and the enrichment factors were 435 and 460, respectively. Fe3O4@Co-TA was reused ten times without significant reduction of the extraction ability. This method was successfully used for the detection of CV and LCV in fish samples, providing an effective technique for food safety monitoring and quality control.

Natural Polyphenol-Vanadium Oxide Nanozymes for Synergistic Chemodynamic/Photothermal Therapy.

The selection of suitable nanozymes with easy synthesis, tumor specificity, multifunction, and high therapeutics is meaningful for tumor therapy. Herein, a facile one-step assembly approach was employed to successfully prepare a novel kind of natural polyphenol tannic acid (TA) hybrid with mixed valence vanadium oxide nanosheets (TA@VOx NSs). In this system, VOx is assembled with TA through metal-phenolic coordination interaction to both introduce superior peroxidase-like activity and high near infrared (NIR) absorption owing to partial reduction of vanadium from V5+ to V4+ . The presence of mixed valence vanadium oxide in TA@VOx NSs is proved to be the key for the catalytic reaction of hydrogen peroxide (H2 O2 ) to . OH, and the corresponding catalytic mechanism of H2 O2 by TA@VOx NSs is proposed. Benefitting from such peroxidase-like activity of TA@VOx NSs, the overproduced H2 O2 of the tumor microenvironment allows the realization of tumor-specific chemodynamic therapy (CDT). As a valid supplement to CDT, the NIR absorption enables TA@VOx NSs to have NIR light-mediated conversion ability for photothermal therapy (PTT) of cancers. Furthermore, in vitro and in vivo experiments confirmed that TA@VOx NSs can effectively inhibit the growth of tumors by synergistic CDT/PTT. These results offer a promising way to develop novel vanadium oxide-based nanozymes for enhanced synergistic tumor-specific treatment.

Atomic-Distributed Coordination State of Metal-Phenolic Compounds Enabled Low Temperature Graphitization for High-Performance Multioriented Graphite Anode.

Continuous efforts have been made to achieve nanostructured carbon materials with highly ordered graphitic structures using facile synthetic methods. 3D graphite nanoballs (GNBs) are synthesized by the low-temperature pyrolysis of a non-graphitizable precursor, tannic acid (TA). Abundant phenol groups on TA bind to Ni2+ to form metal-phenolic coordination, which renders each Ni cation to be atomically distributed by the TA ligands. Even at low temperatures (1000 °C), highly ordered graphitic structure is promoted by the distributed Ni nanoparticles that act as a graphitization catalyzer. The crystallinity of the GNB is fully corroborated by the intense 2D peak observed in Raman spectroscopy. In particular, the graphitic layers have orientations pointing toward multidirections, which are beneficial for the rapid transport of Li-ions into graphite grains. The resulting materials exhibit outstanding electrochemical performance (120 mAh g-1 at 5 C and 282 mAh g-1 at 0.5 C after 500 cycles) when evaluated as a fast-chargeable negative electrode for lithium ion batteries.

Synergistic Effect of Metal-Organic Framework/Gallic Acid in Enhanced Laser Desorption/Ionization Mass Spectrometry.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has become an indispensable tool for high-throughput analysis of macromolecules, but many challenges still remain in detection of small molecules due to the severe matrix-related background interference in the low-molecular-weight ranges (MW < 700 Da). Herein, a gallic acid (GA)-functionalized zirconium 1,4-dicarboxybenzene metal-organic framework (MOF) (denoted as UiO-66-GA) was designed to serve as a new substrate, and a novel strategy on the basis of the synergistic effect of MOF and GA was developed to enhance the LDI process. In comparison with conventional organic matrices, the UiO-66-GA substrate showed superior LDI performance in the analysis of a wide variety of molecules including amino acids, unsaturated fatty acids, bisphenols (BPs), oligosaccharides, peptides, protein, and polyethylene glycol (PEG) of various average molecular weights from 200 to 10000. Perfluorooctanoic sulfonate (PFOS) was used to evaluate the ability of quantitative analysis, and its corresponding limit of detection as low as 1 fmol was achieved. High sensitivity and good salt tolerance of the UiO-66-GA-assisted LDI-MS were allowed to determine ultratrace PFOS in the spiked human urine and serum samples. In addition, the synergistic mechanism of MOF and GA in the enhanced LDI process was investigated by comprehensively comparing GA- and its analogue-functionalized UiO-66, and the results revealed that two aspects contributed to the enhanced LDI process: (1) an enhancement in the metal-phenolic coordination system of UiO-66-GA promoted laser absorption and energy transfer; (2) introduction of carboxyl and hydroxyl groups of GA onto UiO-66 facilitated the LDI process in both positive and negative ion modes. This work expands a new domain for the MOF applications and provides a promising alternative for various molecule analyses.

General Synthesis of Mixed Semiconducting Metal Oxide Hollow Spheres with Tunable Compositions for Low-Temperature Chemiresistive Sensing

Metal oxide hollow spheres (MOHSs) with multicomponent metal elements exhibit intriguing properties due to the synergistic effects of different components. However, it remains a great challenge to develop a general method to synthesize multicomponent MOHSs due to the different hydrolysis and condensation rates of precursors for different metal oxides. Herein, we demonstrate a general strategy for the controllable synthesis of MOHSs with up to five metal elements by decomposition of metal-phenolic coordination polymers (MPCPs), which are prepared by chelation of tannic acid with various metal ions. After calcination to burn out the organic component and induce heterogeneous contraction of MPCPs, a series of MOHSs with multishell structure, high specific surface area (55-171 m2/g), and crystalline mesoporous framework are synthesized, including binary (Fe-Co, Ni-Zn, and Ni-Co oxides), ternary (Ni-Co-Mn and Ni-Co-Zn oxides), and quinary (Ni-Co-Fe-Cu-Zn oxides) MOHSs. The gas sensing nanodevices based on quinary MOHSs show much higher response (10.91) than those based on single component toward 50 ppm of ethanol at 80 °C with the response/recovery time of 85/160 s. The quinary oxides sensor also displays high selectivity toward ethanol against other interfering gases (e.g., methanol, formadehyde, toluene, methane, and hydrogen) and long-term stability (∼94.0% after 4 weeks), which are extremely favorable for practical applications.

Intelligent Metal-Phenolic Metallogels as Dressings for Infected Wounds

In this study, we report a metallogel developed based on metal-phenolic coordination of natural low-cost polyphenolic molecule and metal ions. Gelation occurs by mixing tannic acid (TA) and group (IV) titanium ions (TiIV) to form TA-TiIV gel. The TA-TiIV gel exhibits good capability to incorporate diverse metal ions by in situ co-gelation. Herein, five antimicrobial metal ions, i.e. ferric (FeIII), copper (CuII), zinc (ZnII), cobalt (CoII) and nickel (NiII) ions, were employed to include in TA-TiIV gels for developing intelligent dressings for infected wounds. The chemical and coordinative structures of TA-TiIV metallogels were characterized by UV-Vis and Fourier-transform infrared (FT-IR) spectroscopies. Cytotoxicity of antimicrobial metallogels was explored by MTT assay with NIH 3T3 fibroblasts. The release of metal ions was evaluated by inductively coupled plasma mass spectrometry (ICP-MS), indicating the different releasing profiles upon the coordinative interactions of metal ions with TA. The formation and disassembly of metallogels are sensitive to the presence of acid and an oxidizer, H2O2, which are substances spontaneously generated in infected wounds due to the metabolic activity of bacteria and the intrinsic immune response. The CuII releasing rates of TA-TiIV-CuII metallogels at different pH values of 5.5, 7.4 and 8.5 have been studied. In addition, addition of H2O2 trigger fast release of CuII as a result of oxidation of galloyl groups in TA. Consequently, the antimicrobial potency of TA-TiIV-CuII metallogels can be simultaneously activated while the wounds are infected and healing. The antimicrobial property of metallogels against Gram-negative Escherichia coli, and Gram-positive Methicillin-Resistant Staphylococcus aureus (USA300) and Staphylococcus epidermidis has been investigated by agar diffusion test. In an animal model, the TA-TiIV-CuII metallogels were applied as dressings for infected wounds, indicating faster recovery in the wound area and extremely lower amount of bacteria around the wounds, compared to TA-TiIV gels and gauze. Accordingly, the intelligent nature derived metallogels is a promising and potential materials for medical applications.

Nanoporous carbon spheres derived from metal-phenolic coordination polymers for supercapacitor and biosensor

The conversion of plant polyphenol to multi-functional nanoporous carbon spheres (NCSs) is desirable and challenging. Tannic acid (TA), as one kind of plant polyphenol, has been regarded as one of potential renewable carbon sources for nanoporous carbon materials. However, the nanoporous carbon materials derived from TA usually show low surface area and irregular morphology, which partially limit their broad applications. Herein, we demonstrate the successful synthesis of NCSs with high surface area (up to 2221 m2/g) and uniform diameter (∼120 nm) by direct carbonization of zinc-phenolic coordination polymer using TA as a carbon source. The zinc contents play an important role in tailoring the porosity of NCSs. The specific surface area of NCSs can be adjusted in the range of 527–2221 m2/g as the zinc contents in the coordination polymers changed from 0 to 8.6 wt%. To verify the multi-functions of NCSs, such carbon spheres are further used as a sensing platform for the analysis of nucleic acid variants with high selectivity and low limit of detection, and electrode material for supercapacitor with high specific capacitance, good capacitance retention, and excellent cyclic stability.

In vivo biocompatibility and immunogenicity of metal-phenolic gelation.

In vivo forming hydrogels are of interest for diverse biomedical applications due to their ease-of-use and minimal invasiveness and therefore high translational potential. Supramolecular hydrogels that can be assembled using metal-phenolic coordination of naturally occurring polyphenols and group IV metal ions (e.g. TiIV or ZrIV) provide a versatile and robust platform for engineering such materials. However, the in situ formation and in vivo response to this new class of materials has not yet been reported. Here, we demonstrate that metal-phenolic supramolecular gelation occurs successfully in vivo and we investigate the host response to the material over 14 weeks. The TiIV-tannic acid materials form stable gels that are well-tolerated following subcutaneous injection. Histology reveals a mild foreign body reaction, and titanium biodistribution studies show low accumulation in distal tissues. Compared to poloxamer-based hydrogels (commonly used for in vivo gelation), TiIV-tannic acid materials show a substantially improved in vitro drug release profile for the corticosteroid dexamethasone (from <1 day to >10 days). These results provide essential in vivo characterization for this new class of metal-phenolic hydrogels, and highlight their potential suitability for biomedical applications in areas such as drug delivery and regenerative medicine.

Sensors: Self‐Template Synthesis of Mesoporous Metal Oxide Spheres with Metal‐Mediated Inner Architectures and Superior Sensing Performance (Adv. Funct. Mater. 51/2018)

In article number 1806144, Jing Wei and co-workers demonstrate a general self-templating strategy for the synthesis of mesoporous metal oxide spheres with tunable compositions and metal-mediated inner architectures via thermal decomposition of metal-phenolic coordination polymers. Such materials can be used as a sensing platform for detection of volatile organic compounds and nucleic acids with high sensitivity and selectivity.

Foe to Friend: Supramolecular Nanomedicines Consisting of Natural Polyphenols and Bortezomib.

Bortezomib (BTZ) is a first-in-class boronate proteasome inhibitor used for cancer therapy, but its therapeutic efficacy is usually inhibited by dietary polyphenols due to boronate-catechol complexation. Benefiting from such dynamic covalent chemistry, herein we describe a novel class of supramolecular nanomedicines by rationally converting natural polyphenols from foe to friend through polyphenol-mediated BTZ assembly strategy. The simple conjugation of BTZ to catechol-containing natural polyphenols via boronate ester bond allows the facile formation of dynamic drug amphiphiles, with pH-dependent assembly/disassembly behaviors under different physiological conditions. Ferric ion was also incorporated into the supramolecular system via metal-phenolic coordination interaction to both introduce bioimaging function and facilitate stability of the supramolecular nanomedicines. Our investigation revealed that the supramolecular nanomedicine consisting of natural polyphenol, BTZ and ferric ion dramatically induced apoptosis on cancer cells and suppressed tumor growth in both subcutaneous and bone tumor models with limited adverse effects. Such natural polyphenol-mediated small drug assembly strategy enables the robust fabrication of supramolecular nanomedicines for efficient delivery and controlled release of BTZ in targeted tumor sites, which could be further employed in other types of boronic acid-containing supramolecular therapeutics toward a wide range of diseases.

Nanoengineering of Poly(ethylene glycol) Particles for Stealth and Targeting.

The assembly of particles composed solely or mainly of poly(ethylene glycol) (PEG) is an emerging area that is gaining increasing interest within bio-nano science. PEG, widely considered to be the "gold standard" among polymers for drug delivery, is providing a platform for exploring fundamental questions and phenomena at the interface between particle engineering and biomedicine. These include the targeting and stealth behaviors of synthetic nanomaterials in biological environments. In this feature article, we discuss recent work in the nanoengineering of PEG particles and explore how they are enabling improved targeting and stealth performance. Specific examples include PEG particles prepared through surface-initiated polymerization, mesoporous silica replication via postinfiltration, and particle assembly through metal-phenolic coordination. This particle class exhibits unique in vivo behavior (e.g., biodistribution and immune cell interactions) and has recently been explored for drug delivery applications.

Sol-Gel Synthesis of Metal-Phenolic Coordination Spheres and Their Derived Carbon Composites.

A formaldehyde-assisted metal-ligand crosslinking strategy is used for the synthesis of metal-phenolic coordination spheres based on sol-gel chemistry. A range of mono-metal (Co, Fe, Al, Ni, Cu, Zn, Ce), bi-metal (Fe-Co, Co-Zn) and multi-metal (Fe-Co-Ni-Cu-Zn) species can be incorporated into the frameworks of the colloidal spheres. The formation of coordination spheres involves the pre-crosslinking of plant polyphenol (such as tannic acid) by formaldehyde in alkaline ethanol/water solvents, followed by the aggregation assembly of polyphenol oligomers via metal-ligand crosslinking. The coordination spheres can be used as sensors for the analysis of nucleic acid variants with single-nucleotide discrimination, and a versatile precursor for electrode materials with high electrocatalytic performance.

Sol–Gel Synthesis of Metal–Phenolic Coordination Spheres and Their Derived Carbon Composites

AbstractA formaldehyde‐assisted metal–ligand crosslinking strategy is used for the synthesis of metal–phenolic coordination spheres based on sol–gel chemistry. A range of mono‐metal (Co, Fe, Al, Ni, Cu, Zn, Ce), bi‐metal (Fe‐Co, Co‐Zn) and multi‐metal (Fe‐Co‐Ni‐Cu‐Zn) species can be incorporated into the frameworks of the colloidal spheres. The formation of coordination spheres involves the pre‐crosslinking of plant polyphenol (such as tannic acid) by formaldehyde in alkaline ethanol/water solvents, followed by the aggregation assembly of polyphenol oligomers via metal–ligand crosslinking. The coordination spheres can be used as sensors for the analysis of nucleic acid variants with single‐nucleotide discrimination, and a versatile precursor for electrode materials with high electrocatalytic performance.

Hypochlorous Acid Promoted Platinum Drug Chemotherapy by Myeloperoxidase-Encapsulated Therapeutic Metal Phenolic Nanoparticles.

This study applies in situ production of hypochlorous acid (HOCl) to improve the therapeutic efficacy of platinum drugs. The phagocytic enzyme myeloperoxidase (MPO) is coated with two functional polyphenol derivatives (platinum prodrug polyphenols and PEG polyphenols) and ferric ion by metal phenolic coordination, which can shield MPO from degradation by other compounds in the blood. Moreover, the platinum prodrug can be reduced to cisplatin in cells and produce hydrogen peroxide (H2O2). The MPO catalyzes the conversion of H2O2 to HOCl in the intercellular environment. The as-prepared MPO Pt PEG nanoparticles (MPP NPs) can be employed as a reactive oxygen species cascade bioreaction to enhance platinum drug therapy. The MPP NPs show prolonged blood circulation and high tumor accumulation as evidenced by 89Zr-based positron emission tomography imaging. The MPP NPs effectively inhibit tumor growth in vivo. As a first-in-class platform to harness the highly toxic HOCl in nanomedicine for cancer therapy, this strategy may open doors for further development of progressive therapeutic systems.

Synthesis of spiny metal–phenolic coordination crystals as a sensing platform for sequence-specific detection of nucleic acids

Metal–phenolic coordination crystals with a spiny surface and tunable compositions are synthesized, and can be used as DNA sensors.

Macroscopically interconnected hierarchically porous carbon monolith by metal-phenolic coordination as an sorbent for multi-scale molecules

This study reports on a simple and efficient strategy to prepare macroscopically assembled nanostructured porous carbon (MNPC) based on metal-phenolic interactions. The abundant coordination sites contained in tannic acid enable to form a stable, interconnected hydrogel dough. The porosity evolution mechanism during carbonization process is studied by temperature programmed desorption-mass spectroscopy. Hierarchical pore structure of the MNPC can be developed by modulating the zinc chloride content. The resulting material provides versatile adsorption behaviors for various ranging from small gas molecules to larger molecules such as dye, oil and organic solvents.