Silica nanoparticle supported lipid bilayers for gene delivery.
Ontology highlight
ABSTRACT:
SUBMITTER: Liu J
PROVIDER: S-EPMC2867086 | biostudies-literature | 2009 Sep
REPOSITORIES: biostudies-literature
Publications
Silica nanoparticle supported lipid bilayers for gene delivery.
Liu Juewen J Stace-Naughton Alison A Brinker C Jeffrey CJ
Chemical communications (Cambridge, England) 20090728 34
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. ...[more]
Similar Datasets
Project description: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.
| S-EPMC3332089 | biostudies-literature
Project description:Mesoporous silica nanoparticle-supported lipid bilayers, or "protocells", exhibit a high loading capacity, enhanced colloidal stability, and peptide-directed, cell-specific uptake, making them especially well-suited for targeted delivery of protein toxins to cancer. Protocells loaded with ricin toxin A-chain (RTA) and targeted to hepatocellular carcinoma cause complete cell death at 30 pM of RTA without affecting the viability of control hepatocytes.
| S-EPMC4119887 | biostudies-literature
Project description:Mixing liposomes with hydrophilic particles induces fusion of the liposome onto the particle surface. Such supported bilayers have been studied extensively as models of the cell membrane, while their applications in drug delivery have not been pursued. In this communication, we report liposome fusion on mesoporous particles as a synergistic means to simultaneously load and seal cargo within the porous core. We find fusion of a cationic lipid (DOTAP) on an anionic silica particle loads an anionic fluorescent dye (calcein) into the particle to a concentration exceeding 100x that in the surrounding medium. The loaded "protocell" particles are taken up efficiently by Chinese hamster ovary cells, where, due to a reduced pH within endosomal compartments, calcein is effectively released. Compared to some other nanoparticle systems, protocells provide a simple construct for cargo loading, sealing, delivery, and release. They promise to serve as useful vectors in nanomedicine.
| S-EPMC2649781 | biostudies-literature
Project description: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.
| S-EPMC7754615 | biostudies-literature
Project description:Many essential cellular processes including endocytosis and vesicle trafficking require alteration of membrane geometry. These changes are usually mediated by proteins that can sense and/or induce membrane curvature. Using spherical nanoparticle supported lipid bilayers (SSLBs), we characterize how SpoVM, a bacterial development factor, interacts with differently curved membranes by magic angle spinning solid-state NMR. Our results demonstrate that SSLBs are an effective system for structural and topological studies of membrane geometry-sensitive molecules.
| S-EPMC4677685 | biostudies-literature
Project description:Biomaterial properties that modulate T cell activation, growth, and differentiation are of significant interest in the field of cellular immunotherapy manufacturing. In this work, a new platform technology that allows for the modulation of various activation particle design parameters important for polyclonal T cell activation is presented. Artificial antigen presenting cells (aAPCs) are successfully created using supported lipid bilayers on various cell-templated silica microparticles with defined membrane fluidity and stimulating antibody density. This panel of aAPCs is used to probe the importance of activation particle shape, size, membrane fluidity, and stimulation antibody density on T cell outgrowth and differentiation. All aAPC formulations are able to stimulate T cell growth, and preferentially promote CD8+ T cell growth over CD4+ T cell growth when compared to commercially available pendant antibody-conjugated particles. T cells cultured with HeLa- and red blood cell-templated aAPCs have a less-differentiated and less-exhausted phenotype than those cultured with spherical aAPCs with matched membrane coatings when cultured for 14 days. These results support continued exploration of silica-supported lipid bilayers as an aAPC platform.
| S-EPMC6394850 | biostudies-literature
Project description:Supported lipid bilayers (SLBs) serve important roles as minimalistic models of cellular membranes in multiple diagnostic and pharmaceutical applications as well as in the strive to gain fundamental insights about their complex biological function. To further expand the utility of SLBs, there is a need to go beyond simple lipid compositions to thereby better mimic the complexity of native cell membranes, while simultaneously retaining their compatibility with a versatile range of analytical platforms. To meet this demand, we have in this work explored SLB formation on PEDOT:PSS/silica nanoparticle composite films and mesoporous silica films, both capable of transporting ions to an underlying conducting PEDOT:PSS film. The SLB formation process was evaluated by using the quartz crystal microbalance with dissipation (QCM-D) monitoring, total internal reflection fluorescence (TIRF) microscopy, and fluorescence recovery after photobleaching (FRAP) for membranes made of pure synthetic lipids with or without the reconstituted membrane protein β-secretase 1 (BACE1) as well as cell-derived native lipid vesicles containing overexpressed BACE1. The mesoporous silica thin film was superior to the PEDOT:PSS/silica nanoparticle composite, providing successful formation of bilayers with high lateral mobility and low defect density even for the most complex native cell membranes.
| S-EPMC8280725 | biostudies-literature
Project description:We report on the use of supported lipid bilayers to reveal dynamics of actin polymerization from a nonpolymerizing subphase via cationic phospholipids. Using varying fractions of charged lipid, lipid mobility, and buffer conditions, we show that dynamics at the nanoscale can be used to control the self-assembly of these structures. In the case of fluid-phase lipid bilayers, the actin adsorbs to form a uniform two-dimensional layer with complete surface coverage whereas gel-phase bilayers induce a network of randomly oriented actin filaments, of lower coverage. Reducing the pH increased the polymerization rate, the number of nucleation events, and the total coverage of actin. A model of the adsorption/diffusion process is developed to provide a description of the experimental data and shows that, in the case of fluid-phase bilayers, polymerization arises equally due to the adsorption and diffusion of surface-bound monomers and the addition of monomers directly from the solution phase. In contrast, in the case of gel-phase bilayers, polymerization is dominated by the addition of monomers from solution. In both cases, the filaments are stable for long times even when the G-actin is removed from the supernatant-making this a practical approach for creating stable lipid-actin systems via self-assembly.
| S-EPMC3838754 | biostudies-literature
Project description:The use of colloid supported lipid bilayers (CSLBs) has recently been extended to create colloidal joints, that enable the assembly of structures with internal degrees of flexibility, and to study lipid membranes on curved and closed geometries. These novel applications of CSLBs rely on previously unappreciated properties: the simultaneous fluidity of the bilayer, lateral mobility of inserted (linker) molecules and colloidal stability. Here we characterize every step in the manufacturing of CSLBs in view of these requirements using confocal microscopy and fluorescence recovery after photobleaching (FRAP). Specifically, we have studied the influence of different particle properties (roughness, surface charge, chemical composition, polymer coating) on the quality and mobility of the supported bilayer. We find that the insertion of lipopolymers in the bilayer can affect its homogeneity and fluidity. We improve the colloidal stability by inserting lipopolymers or double-stranded inert DNA into the bilayer. We include surface-mobile DNA linkers and use FRAP to characterize their lateral mobility both in their freely diffusive and bonded state. Finally, we demonstrate the self-assembly of flexibly linked structures from the CSLBs modified with surface-mobile DNA linkers. Our work offers a collection of experimental tools for working with CSLBs in applications ranging from controlled bottom-up self-assembly to model membrane studies.
| S-EPMC6371764 | biostudies-literature
Project description: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.
| S-EPMC3287066 | biostudies-literature