Chemical and Biomolecular Engineering - Research Publications
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ItemDirect Assembly of Metal-Phenolic Network Nanoparticles for Biomedical Applications(Wiley, 2023-11-06)Coordination assembly offers a versatile means to developing advanced materials for various applications. However, current strategies for assembling metal-organic networks into nanoparticles (NPs) often face challenges such as the use of toxic organic solvents, cytotoxicity because of synthetic organic ligands, and complex synthesis procedures. Herein, we directly assemble metal-organic networks into NPs using metal ions and polyphenols (i.e., metal-phenolic networks (MPNs)) in aqueous solutions without templating or seeding agents. We demonstrate the role of buffers (e.g., phosphate buffer) in governing NP formation and the engineering of the NP physicochemical properties (e.g., tunable sizes from 50 to 270 nm) by altering the assembly conditions. A library of MPN NPs is prepared using natural polyphenols and various metal ions. Diverse functional cargos, including anticancer drugs and proteins with different molecular weights and isoelectric points, are readily loaded within the NPs for various applications (e.g., biocatalysis, therapeutic delivery) by direct mixing, without surface modification, owing to the strong affinity of polyphenols to various guest molecules. This study provides insights into the assembly mechanism of metal-organic complexes into NPs and offers a simple strategy to engineer nanosized materials with desired properties for diverse biotechnological applications.
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ItemEngineering Flexible Metal-Phenolic Networks with Guest Responsiveness via Intermolecular Interactions(WILEY-V C H VERLAG GMBH, 2023-04-24)Flexible metal-organic materials are of growing interest owing to their ability to undergo reversible structural transformations under external stimuli. Here, we report flexible metal-phenolic networks (MPNs) featuring stimuli-responsive behavior to diverse solute guests. The competitive coordination of metal ions to phenolic ligands of multiple coordination sites and solute guests (e.g., glucose) primarily determines the responsive behavior of the MPNs, as revealed experimentally and computationally. Glucose molecules can be embedded into the dynamic MPNs upon mixing, leading to the reconfiguration of the metal-organic networks and thus changes in their physicochemical properties for targeting applications. This study expands the library of stimuli-responsive flexible metal-organic materials and the understanding of intermolecular interactions between metal-organic materials and solute guests, which is essential for the rational design of responsive materials for various applications.
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ItemHighly Stable and Active Flexible Electrocatalysts Derived from Lotus Fibers(WILEY-V C H VERLAG GMBH, 2023-03)Abstract 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.
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ItemPolyphenol-Functionalized Cubosomes as Thrombolytic Drug Carriers(WILEY, 2022-11)The safe administration of thrombolytic agents is a challenge for the treatment of acute thrombosis. Lipid-based nanoparticle drug delivery technologies present opportunities to overcome the existing clinical limitations and deliver thrombolytic therapy with enhanced therapeutic outcomes and safety. Herein, lipid cubosomes are examined as nanocarriers for the encapsulation of thrombolytic drugs. The lipid cubosomes are loaded with the thrombolytic drug urokinase-type plasminogen activator (uPA) and coated with a low-fouling peptide that is incorporated within a metal-phenolic network (MPN). The peptide-containing MPN (pep-MPN) coating inhibits the direct contact of uPA with the surrounding environment, as assessed by an in vitro plasminogen activation assay and an ex vivo whole blood clot degradation assay. The pep-MPN-coated cubosomes prepared with 22 wt% peptide demonstrate a cell membrane-dependent thrombolytic activity, which is attributed to their fusogenic lipid behavior. Moreover, compared with the uncoated lipid cubosomes, the uPA-loaded pep-MPN-coated cubosomes demonstrate significantly reduced nonspecific cell association (<10% of the uncoated cubosomes) in the whole blood assay, a prolonged circulating half-life, and reduced splenic uPA accumulation in mice. These studies confirm the preserved bioactivity and cell membrane-dependent release of uPA within pep-MPN-coated lipid cubosomes, highlighting their potential as a delivery vehicle for thrombolytic drugs.
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ItemSite-Selective Coordination Assembly of Dynamic Metal-Phenolic Networks(WILEY-V C H VERLAG GMBH, 2022-08-22)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.
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ItemNo Preview AvailableAssembly of Metal-Phenolic Networks on Water-Soluble Substrates in Nonaqueous Media(WILEY-V C H VERLAG GMBH, 2022-06)Abstract Interfacial modular assemblies of eco‐friendly metal–phenolic networks (MPNs) are of interest for surface and materials engineering. To date, most MPNs are assembled on water‐stable substrates; however, the self‐assembly of MPNs on highly water‐soluble substrates remains unexplored. Herein, a versatile approach is reported to engineer thickness‐tunable coatings (2–25 µm) on a water‐soluble substrate (i.e., urea) via the self‐assembly of MPNs in a nonaqueous solvent (i.e., acetonitrile). The coordination‐driven assembly of the MPN coatings in the nonaqueous solvent is distinct from that in aqueous systems, as the assembly is only achieved following the addition of urea granules into the iron–tannin solution. The coating occurs relatively rapidly (5–60 min), generating micrometer‐thick coatings from the adsorption of FeIII–TA complexes and micrometer‐sized FeIII–TA particles formed in solution. The straightforward nature of the present fabrication method in generating thick and robust coatings with high stability in nonaqueous environments (including at 60 °C) coupled with the broad range of available naturally abundant polyphenol–metal ion combinations expand the applicability of MPNs as coatings for water‐soluble materials, thus providing new opportunities for their broader application in a range of industrial processes and applications.
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ItemAssembly of Bioactive Nanoparticles via Metal-Phenolic Complexation(Wiley, 2022)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.
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ItemImmobilization and Intracellular Delivery of Structurally Nanoengineered Antimicrobial Peptide Polymers Using Polyphenol-Based Capsules(WILEY-V C H VERLAG GMBH, 2022-02-02)Structurally nanoengineered antimicrobial peptide polymers (SNAPPs) are an emerging class of antimicrobials against multidrug-resistant bacteria. Their encapsulation in particle carriers can improve their therapeutic efficacy by preventing peptide degradation, reducing clearance, and enhancing intracellular delivery and dosage to bacteria-infected host cells. Herein, two template-mediated strategies are reported for immobilizing SNAPPs in microcapsules through 1) complexation of SNAPPs with tannic acid (TA) onto porous CaCO3 templates and subsequent removal of the templates (SNAPP–TA capsules) and 2) adsorption of SNAPPs onto CaCO3 templates and subsequent encapsulation within a metal–phenolic (FeIII–TA) coating and template removal (SNAPP–FeIII–TA capsules). The loading amounts of SNAPPs are 0.8 and 4.4 pg per SNAPP–TA and SNAPP–FeIII–TA capsule, respectively. At pH 7.4, there is sustained release of SNAPPs, which retain high antimicrobial activity with minimum inhibitory concentration values of ≈30 µg mL−1 in Escherichia coli. Both capsule systems are internalized by alveolar macrophages in vitro, with negligible cytotoxicity and are amenable to nebulization, remaining stable in nebulized droplets. This study demonstrates the potential of engineered polyphenol-based capsules for peptide drug immobilization and intracellular delivery, which have prospective application in the pulmonary delivery of antimicrobials against respiratory bacterial infections (e.g., pneumonia, tuberculosis).
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ItemOrigins of Structural Elasticity in Metal-Phenolic Networks Probed by Super-Resolution Microscopy and Multiscale Simulations.(ACS publications, 2022)Metal-phenolic networks (MPNs) are amorphous materials that can be used to engineer functional films and particles. A fundamental understanding of the heat-driven structural reorganization of MPNs can offer opportunities to rationally tune their properties (e.g., size, permeability, wettability, hydrophobicity) for applications such as drug delivery, sensing, and tissue engineering. Herein, we use a combination of single-molecule localization microscopy, theoretical electronic structure calculations, and all-atom molecular dynamics simulations to demonstrate that MPN plasticity is governed by both the inherent flexibility of the metal (FeIII)-phenolic coordination center and the conformational elasticity of the phenolic building blocks (tannic acid, TA) that make up the metal-organic coordination complex. Thermal treatment (heating to 150 °C) of the flexible TA/FeIII networks induces a considerable increase in the number of aromatic π-π interactions formed among TA moieties and leads to the formation of hydrophobic domains. In the case of MPN capsules, 15 min of heating induces structural rearrangements that cause the capsules to shrink (from ∼4 to ∼3 μm), resulting in a thicker (3-fold), less porous, and higher protein (e.g., bovine serum albumin) affinity MPN shell. In contrast, when a simple polyphenol such as gallic acid is complexed with FeIII to form MPNs, rigid materials that are insensitive to temperature changes are obtained, and negligible structural rearrangement is observed upon heating. These findings are expected to facilitate the rational engineering of versatile TA-based MPN materials with tunable physiochemical properties for diverse applications.
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ItemBioresponsive Polyphenol-Based Nanoparticles as Thrombolytic Drug Carriers(AMER CHEMICAL SOC, 2022-01-12)Thrombolytic (clot-busting) therapies with plasminogen activators (PAs) are first-line treatments against acute thrombosis and ischemic stroke. However, limitations such as narrow therapeutic windows, low success rates, and bleeding complications hinder their clinical use. Drug-loaded polyphenol-based nanoparticles (NPs) could address these shortfalls by delivering a more targeted and safer thrombolysis, coupled with advantages such as improved biocompatibility and higher stability in vivo. Herein, a template-mediated polyphenol-based supramolecular assembly strategy is used to prepare nanocarriers of thrombolytic drugs. A thrombin-dependent drug release mechanism is integrated using tannic acid (TA) to cross-link urokinase-type PA (uPA) and a thrombin-cleavable peptide on a sacrificial mesoporous silica template via noncovalent interactions. Following drug loading and template removal, the resulting NPs retain active uPA and demonstrate enhanced plasminogen activation in the presence of thrombin (1.14-fold; p < 0.05). Additionally, they display lower association with macrophage (RAW 264.7) and monocytic (THP-1) cell lines (43 and 7% reduction, respectively), reduced hepatic accumulation, and delayed blood clearance in vivo (90% clearance at 60 min vs 5 min) compared with the template-containing NPs. Our thrombin-responsive, polyphenol-based NPs represent a promising platform for advanced drug delivery applications, with potential to improve thrombolytic therapies.