The Experts below are selected from a list of 8763 Experts worldwide ranked by ideXlab platform
Jeffrey C Brinker - One of the best experts on this subject based on the ideXlab platform.
-
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.
-
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.
-
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.
Franz M Geiger - One of the best experts on this subject based on the ideXlab platform.
-
hydrogen bond networks near Supported Lipid Bilayers from vibrational sum frequency generation experiments and atomistic simulations
Journal of Physical Chemistry B, 2018Co-Authors: Merve Doǧangun, Alicia C Mcgeachy, Paul E Ohno, Dongyue Liang, Naomi Dalchand, Qiang Cui, Franz M GeigerAbstract:We report vibrational sum frequency generation (SFG) spectra in which the C–H stretches of Lipid alkyl tails in fully hydrogenated single- and dual-component Supported Lipid Bilayers are detected along with the O–H stretching continuum above the bilayer. As the salt concentration is increased from ∼10 μM to 0.1 M, the SFG intensities in the O–H stretching region decrease by a factor of 2, consistent with significant absorptive–dispersive mixing between χ(2) and χ(3) contributions to the SFG signal generation process from charged interfaces. A method for estimating the surface potential from the second-order spectral lineshapes (in the OH stretching region) is presented and discussed in the context of choosing truly zero-potential reference states. Aided by atomistic simulations, we find that the strength and orientation distribution of the hydrogen bonds over the purely zwitterionic Bilayers are largely invariant between submicromolar and hundreds of millimolar concentrations. However, specific interactio...
-
single component Supported Lipid Bilayers probed using broadband nonlinear optics
Physical Chemistry Chemical Physics, 2018Co-Authors: Laura L Olenick, Alicia C Mcgeachy, Hilary M Chase, Yun Zhang, Merve Dogangun, Stephanie R Walter, Hongfei Wang, Franz M GeigerAbstract:Broadband SFG spectroscopy is shown to offer considerable advantages over scanning systems in terms of signal-to-noise ratios when probing well-formed single-component Supported Lipid Bilayers formed from zwitterionic Lipids with PC headgroups. The SFG spectra obtained from Bilayers formed from DOPC, POPC, DLPC, DMPC, DPPC and DSPC show a common peak at ∼2980 cm−1, which is subject to interference between the C–H and the O–H stretches from the aqueous phase, while membranes having transition temperatures above the laboratory temperature produce SFG spectra with at least two additional peaks, one at ∼2920 cm−1 and another at ∼2880 cm−1. The results validate spectroscopic and structural data from SFG experiments utilizing asymmetric Bilayers in which one leaflet differs from the other in the extent of deuteration. Differences in H2O–D2O exchange experiments reveal that the lineshapes of the broadband SFG spectra are significantly influenced by interference from OH oscillators in the aqueous phase, even when those oscillators are not probed by the incident infrared light in our broadband setup. In the absence of spectral interference from the OH stretches of the solvent, the alkyl chain terminal methyl group of the bilayer is found to be tilted at an angle of 15° to 35° from the surface normal.
-
resonantly enhanced nonlinear optical probes of oxidized multiwalled carbon nanotubes at Supported Lipid Bilayers
Journal of Physical Chemistry B, 2017Co-Authors: Alicia C Mcgeachy, Laura L Olenick, Julianne M Troiano, Ronald S Lankone, Eric S Melby, Thomas R Kuech, Eseohi Ehimiaghe, Howard D Fairbrother, Joel A Pedersen, Franz M GeigerAbstract:With production of carbon nanotubes surpassing billions of tons per annum, concern about their potential interactions with biological systems is growing. Herein, we utilize second harmonic generation spectroscopy, sum frequency generation spectroscopy, and quartz crystal microbalance with dissipation monitoring to probe the interactions between oxidized multiwalled carbon nanotubes (O-MWCNTs) and Supported Lipid Bilayers composed of phosphoLipids with phosphatidylcholine head groups as the dominant component. We quantify O-MWCNT attachment to Supported Lipid Bilayers under biogeochemically relevant conditions and discern that the interactions occur without disrupting the structural integrity of the Lipid Bilayers for the systems probed. The extent of O-MWCNT sorption was far below a monolayer even at 100 mM NaCl and was independent of the chemical composition of the Supported Lipid bilayer.
-
on electronic and charge interference in second harmonic generation responses from gold metal nanoparticles at Supported Lipid Bilayers
Journal of Physical Chemistry C, 2016Co-Authors: Julianne M Troiano, Thomas R Kuech, Joel A Pedersen, Catherine J Murphy, Robert J Hamers, Ariane M Vartanian, Marco D Torelli, Akash Sen, Lisa M Jacob, Franz M GeigerAbstract:Second harmonic generation (SHG) is useful for studying the properties of interfaces, including the surfaces of nanoparticles and the interaction of nanoparticles with biologically relevant surfaces. Gold nanoparticles at the biological membrane represent a particularly interesting system to be probed by SHG spectroscopy given the rich electronic structure of gold nanoparticles and the charged nature of the nano-bio interface. Here we describe the interplay between the resonant and nonresonant components of the second harmonic response as 4 and 14 nm spherical gold nanoparticles (AuNPs) wrapped in the cationic polyelectrolyte poly(allylamine hydrochloride) (PAH) adsorb to negatively charged Supported Lipid Bilayers. In contrast to the SHG response of 4 nm PAH-AuNPs, that we have shown previously to be dominated by resonance enhancement, the SHG response from the adsorption of the 14 nm PAH-AuNPs, with similar hydrodynamic diameters, to a 9:1 DOPC:DOTAP bilayer is dominated by the nonresonant, interfacial,...
Alain Brisson - One of the best experts on this subject based on the ideXlab platform.
-
formation of solid Supported Lipid Bilayers an integrated view
Langmuir, 2006Co-Authors: Ralf P Richter, Remi Berat, Alain BrissonAbstract:Supported Lipid Bilayers (SLBs) are popular models of cell membranes with potential bio-technological applications. A qualitative understanding of the process of SLB formation after exposure of small Lipid vesicles to a hydrophilic support is now emerging. Recent studies have revealed a stunning variety of effects that can take place during this self-organization process. The ensemble of results in our group has revealed unprecedented insight into intermediates of the SLB-formation process and has helped to identify a number of parameters that are determinant for the Lipid deposition on solid supports. The pathway of Lipid deposition can be tuned by electrostatic interactions and by the presence of calcium. We emphasize the importance of the solid support in the SLB-formation process. Our results suggest that the molecular-level interaction between Lipids and the solid support needs to be considered explicitly, to understand the rupture of vesicles and the formation of SLBs as well as to predict the properties of the resulting SLB. The impact of the SLB-formation process on the quality and the physical properties of the resulting SLB as well as implications for other types of surface-confined Lipid Bilayers are discussed.
-
on the kinetics of adsorption and two dimensional self assembly of annexin a5 on Supported Lipid Bilayers
Biophysical Journal, 2005Co-Authors: Ralf P Richter, Josephine Lai Kee Him, Beatrice Tessier, Celine Tessier, Alain BrissonAbstract:Annexin A5 is a protein that binds to membranes containing negatively charged phosphoLipids in a calcium-dependent manner. We previously found that annexin A5 self-assembles into two-dimensional (2D) crystals on Supported Lipid Bilayers (SLBs) formed on mica while a monolayer of disordered trimers is formed on SLBs on silica. Here, we investigated in detail and correlated the adsorption kinetics of annexin A5 on SLBs, Supported on silica and on mica, with the protein's 2D self-assembly behavior. For this study, quartz crystal microbalance with dissipation monitoring and ellipsometry were combined with atomic force microscopy. We find, in agreement with previous studies, that the adsorption behavior is strongly dependent on the concentration of dioleoylphosphatidylserine (DOPS) in the SLB and the calcium concentration in solution. The adsorption kinetics of annexin A5 are similar on silica-SLBs and on mica-SLBs, when taking into account the difference in accessible DOPS between silica-SLBs and mica-SLBs. In contrast, 2D crystals of annexin A5 form readily on mica-SLBs, even at low protein coverage (≤10%), whereas they are not found on silica-SLBs, except in a narrow range close to maximal coverage. These results enable us to construct the phase diagram for the membrane binding and the states of 2D organization of annexin A5. The protein binds to the membrane in two different fractions, one reversible and the other irreversible, at a given calcium concentration. The adsorption is determined by the interaction of protein monomers with the membrane. We propose that the local membrane environment, as defined by the presence of DOPS, DOPC, and calcium ions, controls the adsorption and reversibility of protein binding.
-
following the formation of Supported Lipid Bilayers on mica a study combining afm qcm d and ellipsometry
Biophysical Journal, 2005Co-Authors: R Richter, Alain BrissonAbstract:Supported Lipid Bilayers (SLBs) are popular models of cell membranes with potential biotechnological applications and an understanding of the mechanisms of SLB formation is now emerging. Here we characterize, by combining atomic force microscopy, quartz crystal microbalance with dissipation monitoring, and ellipsometry, the formation of SLBs on mica from sonicated unilamellar vesicles using mixtures of zwitterionic, negatively and positively charged Lipids. The results are compared with those we reported previously on silica. As on silica, electrostatic interactions were found to determine the pathway of Lipid deposition. However, fundamental differences in the stability of surface-bound vesicles and the mobility of SLB patches were observed, and point out the determining role of the solid support in the SLB-formation process. The presence of calcium was found to have a much more pronounced influence on the Lipid deposition process on mica than on silica. Our results indicate a specific calcium-mediated interaction between dioleoylphosphatidylserine molecules and mica. In addition, we show that the use of PLL-g-PEG modified tips considerably improves the AFM imaging of surface-bound vesicles and bilayer patches and evaluate the effects of the AFM tip on the apparent size and shape of these soft structures.
-
on the effect of the solid support on the interleaflet distribution of Lipids in Supported Lipid Bilayers
Langmuir, 2005Co-Authors: Ralf P Richter, Nicolas Maury, Alain BrissonAbstract:The adsorption and spreading of Lipid vesicles on solid supports has become a popular way to create Supported Lipid Bilayers (SLBs), but little attention has been paid to the possible redistribution of Lipid material between the two leaflets of an SLB. We use the technique of quartz crystal microbalance with dissipation monitoring (QCM-D) to follow the adsorption of prothrombin on SLBs formed from sonicated unilamellar vesicles containing mixtures of dioleoylphosphatidylcholine (DOPC) and dioleoylphospatidylserine (DOPS). The specific interaction of prothrombin with negatively charged Lipids is quantified and serves as a reporter of the content of accessible DOPS in SLBs. We compare results obtained on silica and mica and find that the underlying support can induce substantial redistribution of Lipid material between the two leaflets. In particular, SLBs formed on mica showed a substantially depleted amount of accessible DOPS in the presence of calcium. The mechanisms that lead to the Lipid redistribution process are discussed.
-
The formation of Supported Lipid Bilayers on silica nanoparticles revealed by cryoelectron microscopy
Nano Letters, 2005Co-Authors: Stéphane Mornet, Olivier Lambert, Etienne Duguet, Alain BrissonAbstract:The controlled fabrication of biocompatible devices made of Lipid Bilayers deposited onto flat solid supports presents interest as models of cell membranes as well as for their biotechnological applications. We report here on the formation of Supported Lipid Bilayers on silica nanoparticles (nanoSLBs). The successive steps of the adsorption of Lipid vesicles on nanoparticles and the formation of nanoSLBs are revealed in detail by cryotransmission electron microscopy (cryo-EM). The formation of nanoSLBs was achieved for liposomes with positive, neutral, and low net negative charge, while liposomes with a high net negative charge adsorbed to silica nanoparticles but did not rupture. The nanoSLBs were found to follow faithfully the surface contours of the particles, information yet unavailable for SLB formation on planar solid substrates.
Paul N Durfee - One of the best experts on this subject based on the ideXlab platform.
-
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.
-
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...
-
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.
-
the targeted delivery of multicomponent cargos to cancer cells by nanoporous particle Supported Lipid Bilayers
Nature Materials, 2011Co-Authors: Paul N Durfee, Carlee E Ashley, Eric C Carnes, David Patrick Padilla, Genevieve K Phillips, Page A Brown, Tracey N Hanna, Juewen LiuAbstract:Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-Supported Lipid Bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid Supported Lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes.
Carlee E Ashley - One of the best experts on this subject based on the ideXlab platform.
-
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.
-
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.
-
the targeted delivery of multicomponent cargos to cancer cells by nanoporous particle Supported Lipid Bilayers
Nature Materials, 2011Co-Authors: Paul N Durfee, Carlee E Ashley, Eric C Carnes, David Patrick Padilla, Genevieve K Phillips, Page A Brown, Tracey N Hanna, Juewen LiuAbstract:Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-Supported Lipid Bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid Supported Lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes.
