Bioorthogonal catalysis broadens the functional possibilities of intracellular chemistry. Effecti... more Bioorthogonal catalysis broadens the functional possibilities of intracellular chemistry. Effective delivery and regulation of synthetic catalytic systems in cells are challenging due to the complex intracellular environment and catalyst instability. Here, we report the fabrication of protein-sized bioorthogonal nanozymes through the encapsulation of hydrophobic transition metal catalysts into the monolayer of water-soluble gold nanoparticles. The activity of these catalysts can be reversibly controlled by binding a supramolecular cucurbit[7]uril 'gate-keeper' onto the monolayer surface, providing a biomimetic control mechanism that mimics the allosteric regulation of enzymes. The potential of this gated nanozyme for use in imaging and therapeutic applications was demonstrated through triggered cleavage of allylcarbamates for pro-fluorophore activation and propargyl groups for prodrug activation inside living cells.
Combination therapy employing proteins and small molecules provides access to synergistic treatme... more Combination therapy employing proteins and small molecules provides access to synergistic treatment strategies. Co-delivery of these two payloads is challenging due to the divergent physico-chemical properties of small molecule and protein cargos. Nanoparticle-stabilized nanocapsules (NPSCs) are promising for combination treatment strategies since they have the potential to deliver small molecule drugs and proteins simultaneously into the cytosol. In this study, we loaded paclitaxel into the hydrophobic core of the NPSC and self-assembled caspase-3 and nanoparticles on the capsule surface. The resulting combination NPSCs showed a higher cytotoxicity of than either of the single agent NPSCs, with synergistic action established using combination index values.
Nanostructure-enabled hierarchical assembly holds promise for efficient biocatalyst immobilizatio... more Nanostructure-enabled hierarchical assembly holds promise for efficient biocatalyst immobilization for improved stability in bioprocessing. In this work we demonstrate the use of a hierarchical assembly immobilization strategy to enhance the physicochemical properties and stability of lipase B from Candida antarctica (CaLB). CaLB was complexed with iron oxide nanoparticles followed by interfacial assembly at the surface of an oil-in-water emulsion. Subsequent ring opening polymerization of the oil provided cross-linked microparticles that displayed an increase in catalytic efficiency when compared to the native enzyme and Novozym 435. The hierarchical immobilized enzyme assembly showed no leakage from the support in 50% acetonitrile and could be magnetically recovered across five cycles. Immobilized lipase exhibited enhanced thermal and pH stability, providing 72% activity retention after 24 h at 50 °C (pH 7.0) and 62% activity retention after 24 h at pH 3.0 (30 °C); conditions resulting in complete deactivation of the native lipase.
The elastic modulus of an ultrathin nanoparticle (NP) monolayer film is tuned by modulating the b... more The elastic modulus of an ultrathin nanoparticle (NP) monolayer film is tuned by modulating the binding strength between the NPs on a molecular level. NP monolayer films constructed by crosslinking NPs of different binding affinities are fabricated at oil/water interfaces. By inducing buckling patterns on these films, the correlation between the binding affinity of the NPs and the elastic modulus is investigated.
Catalytically active iron oxide nanoparticles are used as recognition elements and signal amplifi... more Catalytically active iron oxide nanoparticles are used as recognition elements and signal amplifiers for the array-based colorimetric sensing of proteins. Interactions between cationic monolayers on the Fe(3) O(4) NPs and analyte proteins differentially modulates the peroxidase-like activity of Fe(3) O(4) NPs, affording catalytically amplified colorimetric signal patterns that enable the detection and identification of proteins at 50 nM.
Functionalized magnetic nanoparticles (MNPs) have been characterized by laser desorption/ionizati... more Functionalized magnetic nanoparticles (MNPs) have been characterized by laser desorption/ionization mass spectrometry (LDI-MS). Quantitative information about surface ligand composition and structure for monolayer and mixed monolayer protected Fe3O4 and FePt NPs can be obtained rapidly with very little sample consumption.
Emulsions stabilized by enzyme-nanoparticle (NP) complexes were used to fabricate robust biocatal... more Emulsions stabilized by enzyme-nanoparticle (NP) complexes were used to fabricate robust biocatalytic scaffolds after core solidification via crosslinking. These biocatalysts feature ease of formation, high retention of enzymatic activity and reusability.
Multifunctional self-assembled systems present platforms for fundamental research and practical a... more Multifunctional self-assembled systems present platforms for fundamental research and practical applications, providing tunability of structure, functionality and stimuli response. Pragmatic structures for biological applications have multiple design requirements, including control of size, stability and environmental response. Here we present the fabrication of multifunctional nanoparticle-stabilized capsules (NPSCs) using a set of orthogonal supramolecular interactions. In these capsules, fluorescent proteins are attached to quantum dots through polyhistidine coordination. These anionic assemblies interact laterally with cationic gold nanoparticles that are anchored to the fatty acid core through guanidinium-carboxylate interactions. The lipophilic core then provides a reservoir for hydrophobic endosome-disrupting agents, generating a system featuring stimuli-responsive payload release into the cytosol with fluorescent monitoring. Keywords multifunctionality; nanocapsules; supramolecular interactions; self-assembly; stimuli-responsive release Multifunctional nanomaterials are important platforms for "smart" applications, combining the properties of their components [ 1 ] to provide synergistic systems [ 2 ] capable of achieving multiple objectives. Through the appropriate choice of attributes, multifunctional materials can overcome challenges that cannot be solved by their individual components, [3] including the ability to dynamically adjust their properties and functions in response to both endogenous [ 4 ] and external environmental stimuli. Several construction challenges, however, must be addressed for these systems to be useful, such as control over the size, stability and dynamic properties. [6] Many systems used for bionanotechnology employ covalent conjugation approaches to generate stable nanostructures. [ 7 ] However, these building elements are fixed, making it
Intracellular protein delivery is an important tool for both therapeutic and fundamental applicat... more Intracellular protein delivery is an important tool for both therapeutic and fundamental applications. Effective protein delivery faces two major challenges: efficient cellular uptake and avoiding endosomal sequestration. We report here a general strategy for direct delivery of functional proteins to the cytosol using nanoparticle-stabilized capsules (NPSCs). These NPSCs are formed and stabilized through supramolecular interactions between the nanoparticle, the protein cargo, and the fatty acid capsule interior.
Bioorthogonal catalysis broadens the functional possibilities of intracellular chemistry. Effecti... more Bioorthogonal catalysis broadens the functional possibilities of intracellular chemistry. Effective delivery and regulation of synthetic catalytic systems in cells are challenging due to the complex intracellular environment and catalyst instability. Here, we report the fabrication of protein-sized bioorthogonal nanozymes through the encapsulation of hydrophobic transition metal catalysts into the monolayer of water-soluble gold nanoparticles. The activity of these catalysts can be reversibly controlled by binding a supramolecular cucurbit[7]uril 'gate-keeper' onto the monolayer surface, providing a biomimetic control mechanism that mimics the allosteric regulation of enzymes. The potential of this gated nanozyme for use in imaging and therapeutic applications was demonstrated through triggered cleavage of allylcarbamates for pro-fluorophore activation and propargyl groups for prodrug activation inside living cells.
Combination therapy employing proteins and small molecules provides access to synergistic treatme... more Combination therapy employing proteins and small molecules provides access to synergistic treatment strategies. Co-delivery of these two payloads is challenging due to the divergent physico-chemical properties of small molecule and protein cargos. Nanoparticle-stabilized nanocapsules (NPSCs) are promising for combination treatment strategies since they have the potential to deliver small molecule drugs and proteins simultaneously into the cytosol. In this study, we loaded paclitaxel into the hydrophobic core of the NPSC and self-assembled caspase-3 and nanoparticles on the capsule surface. The resulting combination NPSCs showed a higher cytotoxicity of than either of the single agent NPSCs, with synergistic action established using combination index values.
Nanostructure-enabled hierarchical assembly holds promise for efficient biocatalyst immobilizatio... more Nanostructure-enabled hierarchical assembly holds promise for efficient biocatalyst immobilization for improved stability in bioprocessing. In this work we demonstrate the use of a hierarchical assembly immobilization strategy to enhance the physicochemical properties and stability of lipase B from Candida antarctica (CaLB). CaLB was complexed with iron oxide nanoparticles followed by interfacial assembly at the surface of an oil-in-water emulsion. Subsequent ring opening polymerization of the oil provided cross-linked microparticles that displayed an increase in catalytic efficiency when compared to the native enzyme and Novozym 435. The hierarchical immobilized enzyme assembly showed no leakage from the support in 50% acetonitrile and could be magnetically recovered across five cycles. Immobilized lipase exhibited enhanced thermal and pH stability, providing 72% activity retention after 24 h at 50 °C (pH 7.0) and 62% activity retention after 24 h at pH 3.0 (30 °C); conditions resulting in complete deactivation of the native lipase.
The elastic modulus of an ultrathin nanoparticle (NP) monolayer film is tuned by modulating the b... more The elastic modulus of an ultrathin nanoparticle (NP) monolayer film is tuned by modulating the binding strength between the NPs on a molecular level. NP monolayer films constructed by crosslinking NPs of different binding affinities are fabricated at oil/water interfaces. By inducing buckling patterns on these films, the correlation between the binding affinity of the NPs and the elastic modulus is investigated.
Catalytically active iron oxide nanoparticles are used as recognition elements and signal amplifi... more Catalytically active iron oxide nanoparticles are used as recognition elements and signal amplifiers for the array-based colorimetric sensing of proteins. Interactions between cationic monolayers on the Fe(3) O(4) NPs and analyte proteins differentially modulates the peroxidase-like activity of Fe(3) O(4) NPs, affording catalytically amplified colorimetric signal patterns that enable the detection and identification of proteins at 50 nM.
Functionalized magnetic nanoparticles (MNPs) have been characterized by laser desorption/ionizati... more Functionalized magnetic nanoparticles (MNPs) have been characterized by laser desorption/ionization mass spectrometry (LDI-MS). Quantitative information about surface ligand composition and structure for monolayer and mixed monolayer protected Fe3O4 and FePt NPs can be obtained rapidly with very little sample consumption.
Emulsions stabilized by enzyme-nanoparticle (NP) complexes were used to fabricate robust biocatal... more Emulsions stabilized by enzyme-nanoparticle (NP) complexes were used to fabricate robust biocatalytic scaffolds after core solidification via crosslinking. These biocatalysts feature ease of formation, high retention of enzymatic activity and reusability.
Multifunctional self-assembled systems present platforms for fundamental research and practical a... more Multifunctional self-assembled systems present platforms for fundamental research and practical applications, providing tunability of structure, functionality and stimuli response. Pragmatic structures for biological applications have multiple design requirements, including control of size, stability and environmental response. Here we present the fabrication of multifunctional nanoparticle-stabilized capsules (NPSCs) using a set of orthogonal supramolecular interactions. In these capsules, fluorescent proteins are attached to quantum dots through polyhistidine coordination. These anionic assemblies interact laterally with cationic gold nanoparticles that are anchored to the fatty acid core through guanidinium-carboxylate interactions. The lipophilic core then provides a reservoir for hydrophobic endosome-disrupting agents, generating a system featuring stimuli-responsive payload release into the cytosol with fluorescent monitoring. Keywords multifunctionality; nanocapsules; supramolecular interactions; self-assembly; stimuli-responsive release Multifunctional nanomaterials are important platforms for "smart" applications, combining the properties of their components [ 1 ] to provide synergistic systems [ 2 ] capable of achieving multiple objectives. Through the appropriate choice of attributes, multifunctional materials can overcome challenges that cannot be solved by their individual components, [3] including the ability to dynamically adjust their properties and functions in response to both endogenous [ 4 ] and external environmental stimuli. Several construction challenges, however, must be addressed for these systems to be useful, such as control over the size, stability and dynamic properties. [6] Many systems used for bionanotechnology employ covalent conjugation approaches to generate stable nanostructures. [ 7 ] However, these building elements are fixed, making it
Intracellular protein delivery is an important tool for both therapeutic and fundamental applicat... more Intracellular protein delivery is an important tool for both therapeutic and fundamental applications. Effective protein delivery faces two major challenges: efficient cellular uptake and avoiding endosomal sequestration. We report here a general strategy for direct delivery of functional proteins to the cytosol using nanoparticle-stabilized capsules (NPSCs). These NPSCs are formed and stabilized through supramolecular interactions between the nanoparticle, the protein cargo, and the fatty acid capsule interior.
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Papers by Youngdo Jeong