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Jeffrey C Brinker - One of the best experts on this subject based on the ideXlab platform.
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Conversion of Metal–Organic Cage to Ligand-Free Ultrasmall Noble Metal Nanocluster Catalysts Confined within Mesoporous Silica Nanoparticle Supports
2019Co-Authors: Wei Zhu, Achraf Noureddine, Jane Y. Howe, Jimin Guo, Jeffrey C BrinkerAbstract:Supported ultrasmall noble metal nanocluster-based (UNMN-based) catalysts are one of the most important classes of solid materials for heterogeneous catalysis. In this work, we present a novel strategy for the controlled synthesis of ligand-free UNMN nanocatalysts based on in situ reduction of a palladium-based (Pd-based) metal–organic cage (MOC) confined within monosized, thiol-modified mesoporous Silica Nanoparticle (MSN) supports. By taking advantage of the high mutual solubility of MOCs and MSNs in DMSO and the strong interactions between the thiol-modified MSN pore wall and MOC surface, a good dispersion of MOC molecules was achieved throughout the MSN support. The close correspondence of the MSN pore diameter (ca. 5.0 nm) with the diameter of the MOC (ca. 4.0 nm) confines MOC packing to approximately a monolayer. Based on this spatial constraint and electrostatic binding of the MOC to the thiol-modified MSN pore surface, in situ MOC reduction followed by metal atom diffusion, coalescence, and anchoring on the active sites resulted in ligand-free Pd-based UNMNs of approximately 0.9 ± 0.2 nm in diameter decorating the MSN pore surfaces. Control experiments of the reduction of a conventional palladium source or the reduction of free, unconstrained cages in solution under the same conditions only produced large metal nanocrystals (NP, >2 nm), confirming the importance of confined reduction to achieve a highly catalytically active surface. In light of this strategy, two catalytic experiments including the reaction of 4-nitrophenol to 4-aminophenol and the Suzuki C–C coupling reaction show superior catalytic activity of the engineered MSN-supported UNMN nanocatalysts compared to their free form and state of the art commercial catalysts. We believe that our new strategy will open new avenues for artificially designed UNMN-inspired nanoarchitectures for wide applications
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uptake and intracellular fate of cholera toxin subunit b modified mesoporous Silica Nanoparticle supported lipid bilayers aka protocells in motoneurons
Nanomedicine: Nanotechnology Biology and Medicine, 2018Co-Authors: Maria Gonzalez A Porras, Paul N Durfee, Jeffrey C Brinker, Sebastian Giambini, Gary C Sieck, Carlos B MantillaAbstract:Cholera toxin B (CTB) modified mesoporous Silica Nanoparticle supported lipid bilayers (CTB-protocells) are a promising, customizable approach for targeting therapeutic cargo to motoneurons. In the present study, the endocytic mechanism and intracellular fate of CTB-protocells in motoneurons were examined to provide information for the development of therapeutic application and cargo delivery. Pharmacological inhibitors elucidated CTB-protocells endocytosis to be dependent on the integrity of lipid rafts and macropinocytosis. Using immunofluorescence techniques, live confocal and transmission electron microscopy, CTB-protocells were primarily found in the cytosol, membrane lipid domains and Golgi. There was no difference in the amount of motoneuron activity dependent uptake of CTB-protocells in neuromuscular junctions, consistent with clathrin activation at the axon terminals during low frequency activity. In conclusion, CTB-protocells uptake is mediated principally by lipid rafts and macropinocytosis. Once internalized, CTB-protocells escape lysosomal degradation, and engage biological pathways that are not readily accessible by untargeted delivery methods.
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protocells modular mesoporous Silica Nanoparticle supported lipid bilayers for drug delivery
Small, 2016Co-Authors: Kimberly S Butler, Paul N Durfee, Christophe Theron, Carlee E Ashley, Eric C Carnes, Jeffrey C BrinkerAbstract:Mesoporous Silica Nanoparticle-supported lipid bilayers, termed ‘protocells,’ represent a potentially transformative class of therapeutic and theranostic delivery vehicle. The field of targeted drug delivery poses considerable challenges that cannot be addressed with a single ‘magic bullet’. Consequently, the protocell has been designed as a modular platform composed of interchangeable biocompatible components. The mesoporous Silica core has variable size and shape to direct biodistribution and a controlled pore size and surface chemistry to accommodate diverse cargo. The encapsulating supported lipid bilayer can be modified with targeting and trafficking ligands as well as polyethylene glycol (PEG) to effect selective binding, endosomal escape of cargo, drug efflux prevention, and potent therapeutic delivery, while maintaining in vivo colloidal stability. This review describes the individual components of the platform, including the mesoporous Silica Nanoparticle core and supported lipid bilayer, their assembly (by multiple techniques) into a protocell, and the combined, often synergistic, performance of the protocell based on in vitro and in vivo studies, including the assessment of biocompatibility and toxicity. In closing, the many emerging variations of the protocell theme and the future directions for protocell research are commented on.
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mesoporous Silica Nanoparticle nanocarriers biofunctionality and biocompatibility
Accounts of Chemical Research, 2013Co-Authors: Derrick Tarn, Eric C Carnes, Jeffrey I Zink, Carlee Erin Ashley, Jeffrey C BrinkerAbstract:The study of ordered mesoporous Silica materials has exploded since their discovery by Mobil researchers 20 years ago. The ability to make uniformly sized, porous, and dispersible Nanoparticles using colloidal chemistry and evaporation-induced self-assembly has led to many applications of mesoporous Silica Nanoparticles (MSNPs) as "nanocarriers" for delivery of drugs and other cargos to cells. The exceptionally high surface area of MSNPs, often exceeding 1000 m²/g, and the ability to independently modify pore size and surface chemistry, enables the loading of diverse cargos and cargo combinations at levels exceeding those of other common drug delivery carriers such as liposomes or polymer conjugates. This is because noncovalent electrostatic, hydrogen-bonding, and van der Waals interactions of the cargo with the MSNP internal surface cause preferential adsorption of cargo to the MSNP, allowing loading capacities to surpass the solubility limit of a solution or that achievable by osmotic gradient loading. The ability to independently modify the MSNP surface and interior makes possible engineered biofunctionality and biocompatibility. In this Account, we detail our recent efforts to develop MSNPs as biocompatible nanocarriers (Figure 1 ) that simultaneously display multiple functions including (1) high visibility/contrast in multiple imaging modalities, (2) dispersibility, (3) binding specificity to a particular target tissue or cell type, (4) ability to load and deliver large concentrations of diverse cargos, and (5) triggered or controlled release of cargo. Toward function 1, we chemically conjugated fluorescent dyes or incorporated magnetic Nanoparticles to enable in vivo optical or magnetic resonance imaging. For function 2, we have made MSNPs with polymer coatings, charged groups, or supported lipid bilayers, which decrease aggregation and improve stability in saline solutions. For functions 3 and 4, we have enhanced passive bioaccumulation via the enhanced permeability and retention effect by modifying the MSNP surfaces with positively charged polymers. We have also chemically attached ligands to MSNPs that selectively bind to receptors overexpressed in cancer cells. We have used encapsulation of MSNPs within reconfigurable supported lipid bilayers to develop new classes of responsive nanocarriers that actively interact with the target cell. Toward function 4, we exploit the high surface area and tailorable surface chemistry of MSNPs to retain hydrophobic drugs. Finally, for function 5, we have engineered dynamic behaviors by incorporating molecular machines within or at the entrances of MSNP pores and by using ligands, polymers, or lipid bilayers. These provide a means to seal-in and retain cargo and to direct MSNP interactions with and internalization by target cells. Application of MSNPs as nanocarriers requires biocompatibility and low toxicity. Here the intrinsic porosity of the MSNP surface reduces the extent of hydrogen bonding or electrostatic interactions with cell membranes as does surface coating with polymers or lipid bilayers. Furthermore, the high surface area and low extent of condensation of the MSNP siloxane framework promote a high rate of dissolution into soluble silicic acid species, which are found to be nontoxic. Potential toxicity is further mitigated by the high drug capacity of MSNPs, which greatly reduces needed dosages compared with other nanocarriers. We anticipate that future generations of MSNPs incorporating molecular machines and encapsulated by membrane-like lipid bilayers will achieve a new level of controlled cellular interactions.
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Silica Nanoparticle supported lipid bilayers for gene delivery
Chemical Communications, 2009Co-Authors: Juewen Liu, Alison Stacenaughton, Jeffrey C BrinkerAbstract:Silica Nanoparticle supported cationic lipids can effectively bind plasmid DNAs and transfect mammalian cells with an efficiency that depends on both the particle size and lipid composition; here the gene delivery and expression process has been confirmed by confocal fluorescence microscopy.
Luru Dai - One of the best experts on this subject based on the ideXlab platform.
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near infrared light powered janus mesoporous Silica Nanoparticle motors
Journal of the American Chemical Society, 2016Co-Authors: Mingjun Xuan, Jingxin Shao, Luru DaiAbstract:We describe fuel-free, near-infrared (NIR)-driven Janus mesoporous Silica Nanoparticle motors (JMSNMs) with diameters of 50, 80, and 120 nm. The Janus structure of the JMSNMs is generated by vacuum sputtering of a 10 nm Au layer on one side of the MSNMs. Upon exposure to an NIR laser, a localized photothermal effect on the Au half-shells results in the formation of thermal gradients across the JMSNMs; thus, the generated self-thermophoresis can actively drive the nanomotors to move at an ultrafast speed, for instance, up to 950 body lengths/s for 50 nm JMSNMs under an NIR laser power of 70.3 W/cm2. The reversible “on/off” motion of the JMSNMs and their directed movement along the light gradient can be conveniently modulated by a remote NIR laser. Moreover, dynamic light scattering measurements are performed to investigate the coexisting translational and rotational motion of the JMSNMs in the presence of both self-thermophoretic forces and strong Brownian forces. These NIR-powered nanomotors demonstrate a...
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near infrared light powered janus mesoporous Silica Nanoparticle motors
Journal of the American Chemical Society, 2016Co-Authors: Mingjun Xuan, Jingxin Shao, Luru DaiAbstract:We describe fuel-free, near-infrared (NIR)-driven Janus mesoporous Silica Nanoparticle motors (JMSNMs) with diameters of 50, 80, and 120 nm. The Janus structure of the JMSNMs is generated by vacuum sputtering of a 10 nm Au layer on one side of the MSNMs. Upon exposure to an NIR laser, a localized photothermal effect on the Au half-shells results in the formation of thermal gradients across the JMSNMs; thus, the generated self-thermophoresis can actively drive the nanomotors to move at an ultrafast speed, for instance, up to 950 body lengths/s for 50 nm JMSNMs under an NIR laser power of 70.3 W/cm(2). The reversible "on/off" motion of the JMSNMs and their directed movement along the light gradient can be conveniently modulated by a remote NIR laser. Moreover, dynamic light scattering measurements are performed to investigate the coexisting translational and rotational motion of the JMSNMs in the presence of both self-thermophoretic forces and strong Brownian forces. These NIR-powered nanomotors demonstrate a novel strategy for overcoming the necessity of chemical fuels and exhibit a significant improvement in the maneuverability of nanomotors while providing potential cargo transportation in a biofriendly manner.
Mingjun Xuan - One of the best experts on this subject based on the ideXlab platform.
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near infrared light powered janus mesoporous Silica Nanoparticle motors
Journal of the American Chemical Society, 2016Co-Authors: Mingjun Xuan, Jingxin Shao, Luru DaiAbstract:We describe fuel-free, near-infrared (NIR)-driven Janus mesoporous Silica Nanoparticle motors (JMSNMs) with diameters of 50, 80, and 120 nm. The Janus structure of the JMSNMs is generated by vacuum sputtering of a 10 nm Au layer on one side of the MSNMs. Upon exposure to an NIR laser, a localized photothermal effect on the Au half-shells results in the formation of thermal gradients across the JMSNMs; thus, the generated self-thermophoresis can actively drive the nanomotors to move at an ultrafast speed, for instance, up to 950 body lengths/s for 50 nm JMSNMs under an NIR laser power of 70.3 W/cm2. The reversible “on/off” motion of the JMSNMs and their directed movement along the light gradient can be conveniently modulated by a remote NIR laser. Moreover, dynamic light scattering measurements are performed to investigate the coexisting translational and rotational motion of the JMSNMs in the presence of both self-thermophoretic forces and strong Brownian forces. These NIR-powered nanomotors demonstrate a...
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near infrared light powered janus mesoporous Silica Nanoparticle motors
Journal of the American Chemical Society, 2016Co-Authors: Mingjun Xuan, Jingxin Shao, Luru DaiAbstract:We describe fuel-free, near-infrared (NIR)-driven Janus mesoporous Silica Nanoparticle motors (JMSNMs) with diameters of 50, 80, and 120 nm. The Janus structure of the JMSNMs is generated by vacuum sputtering of a 10 nm Au layer on one side of the MSNMs. Upon exposure to an NIR laser, a localized photothermal effect on the Au half-shells results in the formation of thermal gradients across the JMSNMs; thus, the generated self-thermophoresis can actively drive the nanomotors to move at an ultrafast speed, for instance, up to 950 body lengths/s for 50 nm JMSNMs under an NIR laser power of 70.3 W/cm(2). The reversible "on/off" motion of the JMSNMs and their directed movement along the light gradient can be conveniently modulated by a remote NIR laser. Moreover, dynamic light scattering measurements are performed to investigate the coexisting translational and rotational motion of the JMSNMs in the presence of both self-thermophoretic forces and strong Brownian forces. These NIR-powered nanomotors demonstrate a novel strategy for overcoming the necessity of chemical fuels and exhibit a significant improvement in the maneuverability of nanomotors while providing potential cargo transportation in a biofriendly manner.
Eric C Carnes - One of the best experts on this subject based on the ideXlab platform.
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protocells modular mesoporous Silica Nanoparticle supported lipid bilayers for drug delivery
Small, 2016Co-Authors: Kimberly S Butler, Paul N Durfee, Christophe Theron, Carlee E Ashley, Eric C Carnes, Jeffrey C BrinkerAbstract:Mesoporous Silica Nanoparticle-supported lipid bilayers, termed ‘protocells,’ represent a potentially transformative class of therapeutic and theranostic delivery vehicle. The field of targeted drug delivery poses considerable challenges that cannot be addressed with a single ‘magic bullet’. Consequently, the protocell has been designed as a modular platform composed of interchangeable biocompatible components. The mesoporous Silica core has variable size and shape to direct biodistribution and a controlled pore size and surface chemistry to accommodate diverse cargo. The encapsulating supported lipid bilayer can be modified with targeting and trafficking ligands as well as polyethylene glycol (PEG) to effect selective binding, endosomal escape of cargo, drug efflux prevention, and potent therapeutic delivery, while maintaining in vivo colloidal stability. This review describes the individual components of the platform, including the mesoporous Silica Nanoparticle core and supported lipid bilayer, their assembly (by multiple techniques) into a protocell, and the combined, often synergistic, performance of the protocell based on in vitro and in vivo studies, including the assessment of biocompatibility and toxicity. In closing, the many emerging variations of the protocell theme and the future directions for protocell research are commented on.
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mesoporous Silica Nanoparticle nanocarriers biofunctionality and biocompatibility
Accounts of Chemical Research, 2013Co-Authors: Derrick Tarn, Eric C Carnes, Jeffrey I Zink, Carlee Erin Ashley, Jeffrey C BrinkerAbstract:The study of ordered mesoporous Silica materials has exploded since their discovery by Mobil researchers 20 years ago. The ability to make uniformly sized, porous, and dispersible Nanoparticles using colloidal chemistry and evaporation-induced self-assembly has led to many applications of mesoporous Silica Nanoparticles (MSNPs) as "nanocarriers" for delivery of drugs and other cargos to cells. The exceptionally high surface area of MSNPs, often exceeding 1000 m²/g, and the ability to independently modify pore size and surface chemistry, enables the loading of diverse cargos and cargo combinations at levels exceeding those of other common drug delivery carriers such as liposomes or polymer conjugates. This is because noncovalent electrostatic, hydrogen-bonding, and van der Waals interactions of the cargo with the MSNP internal surface cause preferential adsorption of cargo to the MSNP, allowing loading capacities to surpass the solubility limit of a solution or that achievable by osmotic gradient loading. The ability to independently modify the MSNP surface and interior makes possible engineered biofunctionality and biocompatibility. In this Account, we detail our recent efforts to develop MSNPs as biocompatible nanocarriers (Figure 1 ) that simultaneously display multiple functions including (1) high visibility/contrast in multiple imaging modalities, (2) dispersibility, (3) binding specificity to a particular target tissue or cell type, (4) ability to load and deliver large concentrations of diverse cargos, and (5) triggered or controlled release of cargo. Toward function 1, we chemically conjugated fluorescent dyes or incorporated magnetic Nanoparticles to enable in vivo optical or magnetic resonance imaging. For function 2, we have made MSNPs with polymer coatings, charged groups, or supported lipid bilayers, which decrease aggregation and improve stability in saline solutions. For functions 3 and 4, we have enhanced passive bioaccumulation via the enhanced permeability and retention effect by modifying the MSNP surfaces with positively charged polymers. We have also chemically attached ligands to MSNPs that selectively bind to receptors overexpressed in cancer cells. We have used encapsulation of MSNPs within reconfigurable supported lipid bilayers to develop new classes of responsive nanocarriers that actively interact with the target cell. Toward function 4, we exploit the high surface area and tailorable surface chemistry of MSNPs to retain hydrophobic drugs. Finally, for function 5, we have engineered dynamic behaviors by incorporating molecular machines within or at the entrances of MSNP pores and by using ligands, polymers, or lipid bilayers. These provide a means to seal-in and retain cargo and to direct MSNP interactions with and internalization by target cells. Application of MSNPs as nanocarriers requires biocompatibility and low toxicity. Here the intrinsic porosity of the MSNP surface reduces the extent of hydrogen bonding or electrostatic interactions with cell membranes as does surface coating with polymers or lipid bilayers. Furthermore, the high surface area and low extent of condensation of the MSNP siloxane framework promote a high rate of dissolution into soluble silicic acid species, which are found to be nontoxic. Potential toxicity is further mitigated by the high drug capacity of MSNPs, which greatly reduces needed dosages compared with other nanocarriers. We anticipate that future generations of MSNPs incorporating molecular machines and encapsulated by membrane-like lipid bilayers will achieve a new level of controlled cellular interactions.
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delivery of small interfering rna by peptide targeted mesoporous Silica Nanoparticle supported lipid bilayers
ACS Nano, 2012Co-Authors: Carlee E Ashley, Eric C Carnes, Katharine E Epler, David Patrick Padilla, Genevieve K Phillips, Robert Castillo, Dan C Wilkinson, Brian S Wilkinson, Cameron Burgard, Robin M KalinichAbstract:The therapeutic potential of small interfering RNAs (siRNAs) is severely limited by the availability of delivery platforms that protect siRNA from degradation, deliver it to the target cell with high specificity and efficiency, and promote its endosomal escape and cytosolic dispersion. Here we report that mesoporous Silica Nanoparticle-supported lipid bilayers (or "protocells") exhibit multiple properties that overcome many of the limitations of existing delivery platforms. Protocells have a 10- to 100-fold greater capacity for siRNA than corresponding lipid Nanoparticles and are markedly more stable when incubated under physiological conditions. Protocells loaded with a cocktail of siRNAs bind to cells in a manner dependent on the presence of an appropriate targeting peptide and, through an endocytic pathway followed by endosomal disruption, promote delivery of the silencing nucleotides to the cytoplasm. The expression of each of the genes targeted by the siRNAs was shown to be repressed at the protein level, resulting in a potent induction of growth arrest and apoptosis. Incubation of control cells that lack expression of the antigen recognized by the targeting peptide with siRNA-loaded protocells induced neither repression of protein expression nor apoptosis, indicating the precise specificity of cytotoxic activity. In terms of loading capacity, targeting capabilities, and potency of action, protocells provide unique attributes as a delivery platform for therapeutic oligonucleotides.
Paul N Durfee - One of the best experts on this subject based on the ideXlab platform.
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uptake and intracellular fate of cholera toxin subunit b modified mesoporous Silica Nanoparticle supported lipid bilayers aka protocells in motoneurons
Nanomedicine: Nanotechnology Biology and Medicine, 2018Co-Authors: Maria Gonzalez A Porras, Paul N Durfee, Jeffrey C Brinker, Sebastian Giambini, Gary C Sieck, Carlos B MantillaAbstract:Cholera toxin B (CTB) modified mesoporous Silica Nanoparticle supported lipid bilayers (CTB-protocells) are a promising, customizable approach for targeting therapeutic cargo to motoneurons. In the present study, the endocytic mechanism and intracellular fate of CTB-protocells in motoneurons were examined to provide information for the development of therapeutic application and cargo delivery. Pharmacological inhibitors elucidated CTB-protocells endocytosis to be dependent on the integrity of lipid rafts and macropinocytosis. Using immunofluorescence techniques, live confocal and transmission electron microscopy, CTB-protocells were primarily found in the cytosol, membrane lipid domains and Golgi. There was no difference in the amount of motoneuron activity dependent uptake of CTB-protocells in neuromuscular junctions, consistent with clathrin activation at the axon terminals during low frequency activity. In conclusion, CTB-protocells uptake is mediated principally by lipid rafts and macropinocytosis. Once internalized, CTB-protocells escape lysosomal degradation, and engage biological pathways that are not readily accessible by untargeted delivery methods.
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mesoporous Silica Nanoparticle supported lipid bilayers protocells for active targeting and delivery to individual leukemia cells
ACS Nano, 2016Co-Authors: Paul N Durfee, Kimberly S Butler, Yushen Lin, Darren R Dunphy, Ayse Muniz, Kevin R Humphrey, Amanda J Lokke, Jacob O Agola, Stanley S Chou, Iming ChenAbstract:Many nanocarrier cancer therapeutics currently under development, as well as those used in the clinical setting, rely upon the enhanced permeability and retention (EPR) effect to passively accumulate in the tumor microenvironment and kill cancer cells. In leukemia, where leukemogenic stem cells and their progeny circulate within the peripheral blood or bone marrow, the EPR effect may not be operative. Thus, for leukemia therapeutics, it is essential to target and bind individual circulating cells. Here, we investigate mesoporous Silica Nanoparticle (MSN)-supported lipid bilayers (protocells), an emerging class of nanocarriers, and establish the synthesis conditions and lipid bilayer composition needed to achieve highly monodisperse protocells that remain stable in complex media as assessed in vitro by dynamic light scattering and cryo-electron microscopy and ex ovo by direct imaging within a chick chorioallantoic membrane (CAM) model. We show that for vesicle fusion conditions where the lipid surface area...
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protocells modular mesoporous Silica Nanoparticle supported lipid bilayers for drug delivery
Small, 2016Co-Authors: Kimberly S Butler, Paul N Durfee, Christophe Theron, Carlee E Ashley, Eric C Carnes, Jeffrey C BrinkerAbstract:Mesoporous Silica Nanoparticle-supported lipid bilayers, termed ‘protocells,’ represent a potentially transformative class of therapeutic and theranostic delivery vehicle. The field of targeted drug delivery poses considerable challenges that cannot be addressed with a single ‘magic bullet’. Consequently, the protocell has been designed as a modular platform composed of interchangeable biocompatible components. The mesoporous Silica core has variable size and shape to direct biodistribution and a controlled pore size and surface chemistry to accommodate diverse cargo. The encapsulating supported lipid bilayer can be modified with targeting and trafficking ligands as well as polyethylene glycol (PEG) to effect selective binding, endosomal escape of cargo, drug efflux prevention, and potent therapeutic delivery, while maintaining in vivo colloidal stability. This review describes the individual components of the platform, including the mesoporous Silica Nanoparticle core and supported lipid bilayer, their assembly (by multiple techniques) into a protocell, and the combined, often synergistic, performance of the protocell based on in vitro and in vivo studies, including the assessment of biocompatibility and toxicity. In closing, the many emerging variations of the protocell theme and the future directions for protocell research are commented on.