Efficient Transport Networks in a Dual Electron/Lithium-Conducting Polymeric Composite for Electrochemical Applications

In this work, an all-functional polymer material composed of the electrically conductive poly­(3,4-ethylenedioxythiophene):poly­(4-styrenesulfonic acid) (PEDOT:PSS) and lithium-conducting poly­(ethylene oxide) (PEO) was developed to form a dual conductor for three-dimensional electrodes in electrochemical applications. The composite exhibits enhanced ionic conductivity (∼10^–4 S cm^–1) and, counterintuitively, electronic conductivity (∼45 S cm^–1) with increasing PEO proportion, optimal at a monomer ratio of 20:1 PEO:PEDOT. Microscopy reveals a unique morphology, where PSS interacts favorably with PEO, destabilizing PEDOT to associate into highly branched, interconnected networks that allow for more efficient electronic transport despite relatively low concentrations. Thermal and X-ray techniques affirm that the PSS–PEO domain suppresses crystallinity, explaining the high ionic conductivity. Electrochemical experiments in lithium cell environments indicate stability as a function of cycling and improved overpotential due to dual transport characteristics despite known issues with both individual components

Nanolayered siRNA Dressing for Sustained Localized Knockdown

The success of RNA interference (RNAi) in medicine relies on the development of technology capable of successfully delivering it to tissues of interest. Significant research has focused on the difficult task of systemic delivery of RNAi; however its local delivery could be a more easily realized approach. Localized delivery is of particular interest for many medical applications, including the treatment of localized diseases, the modulation of cellular response to implants or tissue engineering constructs, and the management of wound healing and regenerative medicine. In this work we present an ultrathin electrostatically assembled coating for localized and sustained delivery of short interfering RNA (siRNA). This film was applied to a commercially available woven nylon dressing commonly used for surgical applications and was demonstrated to sustain significant knockdown of protein expression in multiple cell types for more than one week <i>in vitro</i>. Significantly, this coating can be easily applied to a medically relevant device and requires no externally delivered transfection agents for effective delivery of siRNA. These results present promising opportunities for the localized administration of RNAi

Influence of Ammonium Salts on Discharge and Charge of Li–O₂ Batteries

Li–air (O₂) batteries are promising because of their high theoretical energy density. However, these batteries are plagued with numerous challenges, one of which involves modulating the battery discharge process between a solution or surface-driven formation of the desired lithium peroxide (Li₂O₂) discharge product, and the oxidation of Li₂O₂ below 4 V (vs Li/Li⁺). In this work, we show that tetrabutylammonium (TBA) salts dissolved in ether or dimethyl sulfoxide (with no lithium salt present) can be used as a Li–O₂ electrolyte with a lithium metal anode to support Li₂O₂ formation, lead to >500 mV reduction in charging overpotentials at low current rates as compared to that with lithium salt, and support the oxidation of Li₂O₂ during charge. Furthermore, on the basis of results from several spectroscopic techniques, we propose a mechanism that involves electrochemical-induced transformation of TBA to tributylamine at ∼3.55 V, and the formation of a tributylamine oxide intermediate in the presence of O₂ or Li₂O₂ that is responsible for Li₂O₂ oxidation during charging. This mechanism can also be translated to other ionic liquid-based Li–O₂ batteries where significantly low charging potentials are observed. This work showcases an additive that can be used for Li–O₂ batteries to allow for finer control of the discharge process, and the ability of amine oxides to oxidize Li₂O₂

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

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

Mechanical and Transport Properties of Layer-by-Layer Electrospun Composite Proton Exchange Membranes for Fuel Cell Applications

Composite membranes composed of highly conductive and selective layer-by-layer (LbL) films and electrospun fiber mats were fabricated and characterized for mechanical strength and electrochemical selectivity. The LbL component consists of a proton-conducting, methanol-blocking poly­(diallyl dimethyl ammonium chloride)/sulfonated poly­(2,6-dimethyl-1,4-phenylene oxide) (PDAC/sPPO) thin film. The electrospun fiber component consists of poly­(trimethyl hexamethylene terephthalamide) (PA 6(3)­T) fibers in a nonwoven mat of 60–90% porosity. The bare mats were annealed to improve their mechanical properties, which improvements are shown to be retained in the composite membranes. Spray LbL assembly was used as a means for the rapid formation of proton-conducting films that fill the void space throughout the porous electrospun matrix and create a fuel-blocking layer. Coated mats as thin as 15 μm were fabricated, and viable composite membranes with methanol permeabilities 20 times lower than Nafion and through-plane proton selectivity five and a half times greater than Nafion are demonstrated. The mechanical properties of the spray coated electrospun mats are shown to be superior to the LbL-only system and possess intrinsically greater dimensional stability and lower mechanical hysteresis than Nafion under hydrated conditions. The composite proton exchange membranes fabricated here were tested in an operational direct methanol fuel cell. The results show the potential for higher open circuit voltages (OCV) and comparable cell resistances when compared to fuel cells based on Nafion

Understanding the Chemical Stability of Polymers for Lithium–Air Batteries

Recent studies have shown that many aprotic electrolytes used in lithium–air batteries are not stable against superoxide and peroxide species formed upon discharge and charge. However, the stability of polymers often used as binders and as electrolytes is poorly understood. In this work, we select a number of polymers heavily used in the Li–air/Li-ion battery literature, and examine their stability, and the changes in molecular structure in the presence of commercial Li₂O₂. Of the polymers studied, poly­(acrylonitrile) (PAN), poly­(vinyl chloride) (PVC), poly­(vinylidene fluoride) (PVDF), poly­(vinylidene fluoride-<i>co</i>-hexafluoropropylene) (PVDF-HFP), and poly­(vinylpyrrolidone) (PVP) are reactive and unstable in the presence of Li₂O₂. The presence of the electrophilic nitrile group in PAN allows for nucleophilic attack by Li₂O₂ at the nitrile carbon, before further degradation of the polymer backbone. For the halogenated polymers, the presence of the electron-withdrawing halogens and adjacent α and β hydrogen atoms that become electron-deficient due to hyperconjugation makes PVC, PVDF, and PVDF-HFP undergo dehydrohalogenation reactions with Li₂O₂. PVP is also reactive, but with much slower kinetics. On the other hand, the polymers poly­(tetrafluoroethylene) (PTFE), Nafion, and poly­(methyl methacrylate) (PMMA) appear stable against nucleophilic Li₂O₂ attack. The lack of labile hydrogen atoms and the poor leaving nature of the fluoride group allow for the stability of PTFE and Nafion, while the methyl and methoxy functionalities in PMMA reduce the number of potential reaction pathways for Li₂O₂ attack in PMMA. Poly­(ethylene oxide) (PEO) appears relatively stable, but may undergo some cross-linking in the presence of Li₂O₂. Knowledge gained from this work will be essential in selecting and developing new polymers as stable binders and solid or gel electrolytes for lithium–air batteries

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

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–O₂ batteries. We show that applying potentials greater than open circuit voltage (OCV, ∼3 V_Li), which is typically required for Li–O₂ 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

Uncharged Helical Modular Polypeptide Hydrogels for Cellular Scaffolds

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

Tuning Smart Microgel Swelling and Responsive Behavior through Strong and Weak Polyelectrolyte Pair Assembly

The layer-by-layer (LbL) assembly of polyelectrolyte pairs on temperature and pH-sensitive cross-linked poly­(<i>N</i>-isopropylacrylamide)-co-(methacrylic acid), poly­(NIPAAm-co-MAA), microgels enabled a fine-tuning of the gel swelling and responsive behavior according to the mobility of the assembled polyelectrolyte (PE) pair and the composition of the outermost layer. Microbeads with well-defined morphology were initially prepared by synthesis in supercritical carbon dioxide. Upon LbL assembly of polyelectrolytes, interactions between the multilayers and the soft porous microgel led to differences in swelling and thermoresponsive behavior. For the weak PE pairs, namely poly­(l-lysine)/poly­(l-glutamic acid) and poly­(allylamine hydrochloride)/poly­(acrylic acid), polycation-terminated microgels were less swollen and more thermoresponsive than native microgel, whereas polyanion-terminated microgels were more swollen and not significantly responsive to temperature, in a quasi-reversible process with consecutive PE assembly. For the strong PE pair, poly­(diallyldimethylammonium chloride)/poly­(sodium styrene sulfonate), the differences among polycation and polyanion-terminated microgels are not sustained after the first PE bilayer due to extensive ionic cross-linking between the polyelectrolytes. The tendencies across the explored systems became less noteworthy in solutions with larger ionic strength due to overall charge shielding of the polyelectrolytes and microgel. ATR FT-IR studies correlated the swelling and responsive behavior after LbL assembly on the microgels with the extent of H-bonding and alternating charge distribution within the gel. Thus, the proposed LbL strategy may be a simple and flexible way to engineer smart microgels in terms of size, surface chemistry, overall charge and permeability

Enhanced Stability of Polymeric Micelles Based on Postfunctionalized Poly(ethylene glycol)-<i>b</i>-poly(γ-propargyl l-glutamate): The Substituent Effect

One of the major obstacles that delay the clinical translation of polymeric micelle drug delivery systems is whether these self-assembled micelles can retain their integrity in blood following intravenous (IV) injection. The objective of this study was to evaluate the impact of core functionalization on the thermodynamic and kinetic stability of polymeric micelles. The combination of ring-opening polymerization of <i>N</i>-carboxyanhydride (NCA) with highly efficient “click” coupling has enabled easy and quick access to a family of poly­(ethylene glycol)-block-poly­(γ-R-glutamate)­s with exactly the same block lengths, for which the substituent “R” is tuned. The structures of these copolymers were carefully characterized by ¹H NMR, FT-IR, and GPC. When pyrene is used as the fluorescence probe, the critical micelle concentrations (CMCs) of these polymers were found to be in the range of 10^–7–10^–6 M, which indicates good thermodynamic stability for the self-assembled micelles. The incorporation of polar side groups in the micelle core leads to high CMC values; however, micelles prepared from these copolymers are kinetically more stable in the presence of serum and upon SDS disturbance. It was also observed that these polymers could effectively encapsulate paclitaxel (PTX) as a model anticancer drug, and the micelles possessing better kinetic stability showed better suppression of the initial “burst” release and exhibited more sustained release of PTX. These PTX-loaded micelles exerted comparable cytotoxicity against HeLa cells as the clinically approved Cremophor PTX formulation, while the block copolymers showed much lower toxicity compared to the cremophor–ethanol mixture. The present work demonstrated that the <b>PEG-<i>b</i>-PPLG</b> can be a uniform block copolymer platform toward development of polymeric micelle delivery systems for different drugs through the facile modification of the PPLG block