33 research outputs found

    Rationally Designed Polycationic Carriers for Potent Polymeric siRNA-Mediated Gene Silencing

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    The delivery of small interfering RNA (siRNA) remains a major hurdle for the clinical translation of RNA interference (RNAi) therapeutics. Because of its low valency and rigid nature, siRNA typically requires high excesses of cationic delivery materials to package it stably and deliver it to the cytoplasm of target cells, resulting in high toxicities and inefficient gene silencing <i>in vivo</i>. To address these challenges, we pair a polymeric form of siRNA, p-shRNA, with optimized biodegradable polycations to form stable complexes that induce far more potent gene silencing than with siRNA complexes. Furthermore, we unveil a set of design rules governing p-shRNA delivery, using degradable polycations containing hydrophobic and stabilizing polyethylene glycol domains that enable both stable condensation and efficient release inside cells. We demonstrate the therapeutic potential of this approach by silencing the oncogene STAT3 in a well-established B16F10 mouse melanoma model to significantly prolong survival. By blending nucleic acid engineering and polymer design, our system provides a potentially translatable platform for RNAi-based therapies

    Biotemplated Silica and Silicon Materials as Building Blocks for Micro- to Nanostructures

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    Silicon is essential in several energy-related devices, including solar cells, batteries, and some electrochemical systems. These devices often rely on micro- or nanostructures to function efficiently, and require patterning of metallic surfaces. Currently, constructing silicon features at the micro- and nanoscale requires top-down energy-intensive processes, such as e-beam lithography, chemical etching, or anodization. While it is difficult to form silicon in aqueous solution, its oxide, silica, can easily be synthesized using sol–gel chemistry and nucleated onto templates with diverse shapes to create porous or continuous architectures. Here, we demonstrate that novel silica nanostructures can be synthesized via biomineralization, and that they can be reduced to silicon using magnesiothermal reduction. We selected three biotemplates to create silica structures with various aspect ratios and length scales. First, we use diatomaceous earth as a model silica material to optimize our process, and we also biomineralize silica onto two microorganisms, the high aspect ratio M13 bacteriophage, and the helical Spirulina major algae. During our process, the shape of the materials is preserved, resulting in silicon nanowires, nanoporous networks, spirals, and other micro- and nanostructures with high surface area. Our method provides an alternative for the creation of silicon nanostructures, using preformed silica synthesized in solution. The process could be extended to a broader range of microorganisms and metal oxides for the rational design of on-demand micro- and nanostructured metals. In addition, we show that the intrinsic composition of the biotemplates as well as their growth medium can introduce impurities that could potentially be used as dopants in the final silicon structures, and that could allow for tuning the composition of n-doped or p-doped biotemplated silicon for use as semiconducting building blocks

    Uncharged Helical Modular Polypeptide Hydrogels for Cellular Scaffolds

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    Grafted synthetic polypeptides hold appeal for extending the range of biophysical properties achievable in synthetic extracellular matrix (ECM) hydrogels. Here, <i>N</i>-carboxyanhydride polypeptide, poly­(γ-propargyl-l-glutamate) (PPLG) macromers were generated by fully grafting the “clickable” side chains with mixtures of short polyethylene glycol (PEG) chains terminated with inert (−OH) or reactive (maleimide and/or norbornene) groups, then reacting a fraction of these groups with an RGD cell attachment motif. A panel of synthetic hydrogels was then created by cross-linking the PPLG macromers with a 4-arm PEG star molecule. Compared to well-established PEG-only hydrogels, gels containing PPLG exhibited dramatically less dependence on swelling as a function of cross-link density. Further, PPLG-containing gels, which retain an α-helical chain conformation, were more effective than standard PEG gels in fostering attachment of a human mesenchymal stem cell (hMSC) line for a given concentration of RGD in the gel. These favorable properties of PPLG-containing PEG hydrogels suggest they may find broad use in synthetic ECM

    Vapor-Phase Polymerization of Nanofibrillar Poly(3,4-ethylenedioxythiophene) for Supercapacitors

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    Nanostructures of the conducting polymer poly(3,4-ethylene­dioxy­thiophene) with large surface areas enhance the performance of energy storage devices such as electrochemical supercapacitors. However, until now, high aspect ratio nanofibers of this polymer could only be deposited from the vapor-phase, utilizing extrinsic hard templates such as electrospun nanofibers and anodized aluminum oxide. These routes result in low conductivity and require postsynthetic template removal, conditions that stifle the development of conducting polymer electronics. Here we introduce a simple process that overcomes these drawbacks and results in vertically directed high aspect ratio poly(3,4-ethylene­dioxy­thiophene) nanofibers possessing a high conductivity of 130 S/cm. Nanofibers deposit as a freestanding mechanically robust film that is easily processable into a supercapacitor without using organic binders or conductive additives and is characterized by excellent cycling stability, retaining more than 92% of its initial capacitance after 10 000 charge/discharge cycles. Deposition of nanofibers on a hard carbon fiber paper current collector affords a highly efficient and stable electrode for a supercapacitor exhibiting gravimetric capacitance of 175 F/g and 94% capacitance retention after 1000 cycles

    Versatile Three-Dimensional Virus-Based Template for Dye-Sensitized Solar Cells with Improved Electron Transport and Light Harvesting

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    By genetically encoding affinity for inorganic materials into the capsid proteins of the M13 bacteriophage, the virus can act as a template for the synthesis of nanomaterial composites for use in various device applications. Herein, the M13 bacteriophage is employed to build a multifunctional and three-dimensional scaffold capable of improving both electron collection and light harvesting in dye-sensitized solar cells (DSSCs). This has been accomplished by binding gold nanoparticles (AuNPs) to the virus proteins and encapsulating the AuNP–virus complexes in TiO<sub>2</sub> to produce a plasmon-enhanced and nanowire (NW)-based photoanode. The NW morphology exhibits an improved electron diffusion length compared to traditional nanoparticle-based DSSCs, and the AuNPs increase the light absorption of the dye-molecules through the phenomenon of localized surface plasmon resonance. Consequently, we report a virus-templated and plasmon-enhanced DSSC with an efficiency of 8.46%, which is achieved through optimizing both the NW morphology and the concentration of AuNPs loaded into the solar cells. In addition, we propose a theoretical model that predicts the experimentally observed trends of plasmon enhancement

    Drastically Lowered Protein Adsorption on Microbicidal Hydrophobic/Hydrophilic Polyelectrolyte Multilayers

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    Polyelectrolyte multilayer films assembled from a hydrophobic <i>N</i>-alkylated polyethylenimine and a hydrophilic polyacrylate were discovered to exhibit strong antifouling, as well as antimicrobial, activities. Surfaces coated with these layer-by-layer (LbL) films, which range from 6 to 10 bilayers (up to 45 nm in thickness), adsorbed up to 20 times less protein from blood plasma than the uncoated controls. The dependence of the antifouling activity on the nature of the polycation, as well as on assembly conditions and the number of layers in the LbL films, was investigated. Changing the hydrophobicity of the polycation altered the surface composition and the resistance to protein adsorption of the LbL films. Importantly, this resistance was greater for coated surfaces with the polyanion on top; for these films, the average zeta potential pointed to a near neutral surface charge, thus, presumably minimizing their electrostatic interactions with the protein. The film surface exhibited a large contact angle hysteresis, indicating a heterogeneous topology likely due to the existence of hydrophobic–hydrophilic regions on the surface. Scanning electron micrographs of the film surface revealed the existence of nanoscale domains. We hypothesize that the existence of hydrophobic/hydrophilic nanodomains, as well as surface charge neutrality, contributes to the LbL film’s resistance to protein adsorption

    PEG–Polypeptide Block Copolymers as pH-Responsive Endosome-Solubilizing Drug Nanocarriers

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    Herein we report the potential of click chemistry-modified polypeptide-based block copolymers for the facile fabrication of pH-sensitive nanoscale drug delivery systems. PEG–polypeptide copolymers with pendant amine chains were synthesized by combining <i>N</i>-carboxyanhydride-based ring-opening polymerization with post-functionalization using azide–alkyne cycloaddition. The synthesized block copolymers contain a polypeptide block with amine-functional side groups and were found to self-assemble into stable polymersomes and disassemble in a pH-responsive manner under a range of biologically relevant conditions. The self-assembly of these block copolymers yields nanometer-scale vesicular structures that are able to encapsulate hydrophilic cytotoxic agents like doxorubicin at physiological pH but that fall apart spontaneously at endosomal pH levels after cellular uptake. When drug-encapsulated copolymer assemblies were delivered systemically, significant levels of tumor accumulation were achieved, with efficacy against the triple-negative breast cancer cell line, MDA-MB-468, and suppression of tumor growth in an in vivo mouse model

    Multilayer Films Assembled from Naturally-Derived Materials for Controlled Protein Release

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    Herein we designed and characterized films composed of naturally derived materials for controlled release of proteins. Traditional drug delivery strategies rely on synthetic or semisynthetic materials or utilize potentially denaturing assembly conditions that are not optimal for sensitive biologics. Layer-by-layer (LbL) assembly of films uses benign conditions and can generate films with various release mechanisms including hydrolysis-facilitated degradation. These use components such as synthetic polycations that degrade into non-natural products. Herein we report the use of a naturally derived, biocompatible and degradable polyanion, poly­(β-l-malic acid), alone and in combination with chitosan in an LbL film, whose degradation products of malic acid and chitosan are both generally recognized as safe (GRAS) by the FDA. We have found that films based on this polyanion have shown sustained release of a model protein, lysozyme that can be timed from tens of minutes to multiple days through different film architectures. We also report the incorporation and release of a clinically used biologic, basic fibroblast growth factor (bFGF), which demonstrates the use of this strategy as a platform for controlled release of various biologics

    Instability of Poly(ethylene oxide) upon Oxidation in Lithium–Air Batteries

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    The instability of aprotic and polymer electrolytes in Li–air batteries limits the development of these batteries for practical use. Here, we investigate the stability of an electrolyte based on poly­(ethylene oxide) (PEO), which has been used extensively for polymer Li-ion batteries, during discharge and charge of Li–O<sub>2</sub> batteries. We show that applying potentials greater than open circuit voltage (OCV, ∼3 V<sub>Li</sub>), which is typically required for Li–O<sub>2</sub> battery charging, increases the rate of PEO auto-oxidation in an oxygenated environment, with and without prior discharge. Analysis on the rate of reaction, extent of oxidation, and the oxidation products allows us to propose that rate of spontaneous radical formation in PEO is accelerated at applied potentials greater than OCV. We also suggest that the phenomena described here will still occur in ether-based electrolytes at room temperature, albeit at a slower rate, and that this will prevent the use of such electrolytes for practical long-lived Li–air batteries. Therefore, PEO-based electrolytes are unsuitable for use in Li–air batteries
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