Chemical and Biomolecular Engineering - Research Publications
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ItemNo Preview AvailableMetal–Phenolic‐Mediated Assembly of Functional Small Molecules into Nanoparticles: Assembly and Bioapplications(Wiley, 2024-03-18)Abstract Small molecules, including therapeutic drugs and tracer molecules, play a vital role in biological processing, disease treatment and diagnosis, and have inspired various nanobiotechnology approaches to realize their biological function, particularly in drug delivery. Desirable features of a delivery system for functional small molecules (FSMs) include high biocompatibility, high loading capacity, and simple manufacturing processes, without the need for chemical modification of the FSM itself. Herein, we report a simple and versatile approach, based on metal–phenolic‐mediated assembly, for assembling FSMs into nanoparticles (i.e., FSM‐MPN NPs) under aqueous and ambient conditions. We demonstrate loading of anticancer drugs, latency reversal agents, and fluorophores at up to ~80 % that is mostly facilitated by π and hydrophobic interactions between the FSM and nanoparticle components. Secondary nanoparticle engineering involving coating with a polyphenol–antibody thin film or sequential co‐loading of multiple FSMs enables cancer cell targeting and combination delivery, respectively. Incorporating fluorophores into FSM‐MPN NPs enables the visualization of biodistribution at different time points, revealing that most of these NPs are retained in the kidney and heart 24 h post intravenous administration. This work provides a viable pathway for the rational design of small molecule nanoparticle delivery platforms for diverse biological applications.
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ItemMetal-Phenolic-Mediated Assembly of Functional Small Molecules into Nanoparticles: Assembly and Bioapplications(WILEY-V C H VERLAG GMBH, 2024-03-18)Small molecules, including therapeutic drugs and tracer molecules, play a vital role in biological processing, disease treatment and diagnosis, and have inspired various nanobiotechnology approaches to realize their biological function, particularly in drug delivery. Desirable features of a delivery system for functional small molecules (FSMs) include high biocompatibility, high loading capacity, and simple manufacturing processes, without the need for chemical modification of the FSM itself. Herein, we report a simple and versatile approach, based on metal-phenolic-mediated assembly, for assembling FSMs into nanoparticles (i.e., FSM-MPN NPs) under aqueous and ambient conditions. We demonstrate loading of anticancer drugs, latency reversal agents, and fluorophores at up to ~80 % that is mostly facilitated by π and hydrophobic interactions between the FSM and nanoparticle components. Secondary nanoparticle engineering involving coating with a polyphenol-antibody thin film or sequential co-loading of multiple FSMs enables cancer cell targeting and combination delivery, respectively. Incorporating fluorophores into FSM-MPN NPs enables the visualization of biodistribution at different time points, revealing that most of these NPs are retained in the kidney and heart 24 h post intravenous administration. This work provides a viable pathway for the rational design of small molecule nanoparticle delivery platforms for diverse biological applications.
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ItemEngineering Antimicrobial Metal-Phenolic Network Nanoparticles with High Biocompatibility for Wound Healing(WILEY-V C H VERLAG GMBH, 2024-02)Antibiotic-resistant bacteria pose a global health threat by causing persistent and recurrent microbial infections. To address this issue, antimicrobial nanoparticles (NPs) with low drug resistance but potent bactericidal effects have been developed. However, many of the developed NPs display poor biosafety and their synthesis often involves complex procedures and the antimicrobial modes of action are unclear. Herein, a simple strategy is reported for designing antimicrobial metal-phenolic network (am-MPN) NPs through the one-step assembly of a seeding agent (diethyldithiocarbamate), natural polyphenols, and metal ions (e.g., Cu2+ ) in aqueous solution. The Cu2+ -based am-MPN NPs display lower Cu2+ antimicrobial concentrations (by 10-1000 times) lower than most reported nanomaterials and negligible toxicity across various models, including, cells, blood, zebrafish, and mice. Multiple antimicrobial modes of the NPs have been identified, including bacterial wall disruption, reactive oxygen species production, and quinoprotein formation, with the latter being a distinct pathway identified for the antimicrobial activity of the polyphenol-based am-MPN NPs. The NPs exhibit excellent performance against multidrug-resistant bacteria (e.g., methicillin-resistant Staphylococcus aureus (MRSA)), efficiently inhibit and destroy bacterial biofilms, and promote the healing of MRSA-infected skin wounds. This study provides insights on the antimicrobial properties of metal-phenolic materials and the rational design of antimicrobial metal-organic materials.
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ItemCytoprotective Metal-Phenolic Network Sporulation to Modulate Microalgal Mobility and Division(WILEY, 2024-01)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.
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ItemNo Preview AvailableDirect Assembly of Metal‐Phenolic Network Nanoparticles for Biomedical Applications(Wiley, 2023-11-06)Abstract 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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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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ItemPeptide-Based Coacervate Protocells with Cytoprotective Metal-Phenolic Network Membranes(AMER CHEMICAL SOC, 2023-10-03)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.
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ItemSolid-State Encapsulation of Urea via Mechanochemistry-Driven Engineering of Metal-Phenolic Networks(AMER CHEMICAL SOC, 2023-09-07)Controlled-release fertilizers (CRFs) are sustainable alternatives as they can increase crop yield and minimize environmental contamination associated with conventional fertilizers. However, there remains a demand for the development of CRFs with high biocompatibility, and tunable morphologies and mechanical properties. Herein, a solvent-free mechanochemical method is developed for synthesizing urea-encapsulated metal-phenolic networks (urea-MPN matrices) as CRFs. The matrices exhibit tunable mechanical resistance, crystallinity, stiffness, and wettability properties via rearranging the internal structure of the MPNs and their subsequent interaction with the encapsulated urea crystals. Sample aging (7 days) leads to a higher degree of complexation of the MPNs, resulting in a material with increased elasticity and melting point relative to the as-synthesized sample. Thermal treatment (60 °C for 6 h) instigates structural reorganization of the urea crystals within the matrix, generating a more robust material with a 51-fold increase in Young’s modulus. As CRFs, the urea-MPN matrices can be tuned to prolong the release of urea for up to 9 days depending on the treatment applied. As the mechanochemical synthesis of MPNs facilitates the tuning of physiochemical properties and has greater practicability for inclusion within large-scale processing, it has potential implementation within a broad range of industries.
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ItemSupramolecular Assembly of Polyphenols and Nucleic Acids by Thermal Cycling for Immune Cell Activation(American Chemical Society (ACS), 2023)Supramolecular assembly of polyphenols and biomacromolecules (proteins and nucleic acids) has emerged as a versatile and simple strategy to construct nanomaterials with biological activity. Here, we report a strategy to finely control the supramolecular assembly of tannic acid and oligonucleotides into uniform and stable nanoparticles by exploiting the thermal cycling of tannic acid. The equilibrium of complexation is investigated, and individual nanoparticles are resolved with nanoscale resolution by using stochastic optical reconstruction microscopy. The nanoparticles incorporating cytosine phosphoguanine (CpG) oligonucleotides are efficiently taken up by cells and trafficked via endo/lysosomal compartments and induce up to a 7-fold increase in tumor necrosis factor secretion in RAW 264.7 macrophage cells compared with naked CpG oligonucleotides. This work highlights the potential of this simple approach to engineer two-component tannic acid–oligonucleotide nanoparticles for the intracellular delivery of therapeutic nucleic acids.
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ItemPoly(ethylene glycol) Cross-Linked Antibody Nanoparticles for Tunable Biointeractions(American Chemical Society (ACS), 2023)Liver accumulation of nanoparticles is a major challenge in nanoparticle-mediated delivery as it can reduce the delivery of the nanoparticles to their intended site and lead to liver damage and toxicity. Recent studies have shown that particle engineering, e.g., nanoparticle composition, can influence liver uptake and allow homing of nanoparticles to specific organs or tissues. Herein, we investigated the role of nanoparticle cross-linking on liver uptake. We developed a series of antibody nanoparticles (AbNPs) using various poly(ethylene glycol) (PEG) molecule (e.g., different arm numbers and arm lengths) cross-linkers. Specifically, AbNPs based on Herceptin were engineered with PEG cross-linker architectures ranging from 2-arm (at molecular weights of 600 Da, 2.5 kDa, and 5 kDa) to 4-arm and 8-arm via a mesoporous silica templating method. The molecular architecture of PEG modulated not only the targeting ability of the AbNPs in model cell lines but also their interaction with phagocytes in human blood. Increasing the PEG arm length from 600 Da to 5 kDa also reduced the uptake of the nanoparticles in the liver by 85%. Tumor accumulation of Herceptin AbNPs cross-linked with a 5 kDa 2-arm-PEG was 50% higher compared with control AbNPs and displayed similar liver uptake as free Herceptin. This study highlights the role of PEG cross-linking in receptor targeting and liver uptake, which influence tumor targeting, and combined with the versatility and multifunctionality of the antibody nanoparticle platform could lead to the development of organ-selective targeted antibody nanoparticle assemblies.
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