Layer‐by‐Layer Coated Gold Nanoparticles: Size‐Dependent Delivery of DNA into Cells

Because nanoparticles are finding uses in myriad biomedical applications, including the delivery of nucleic acids, a detailed knowledge of their interaction with the biological system is of utmost importance. Here the size‐dependent uptake of gold nanoparticles (AuNPs) (20, 30, 50 and 80 nm), coated with a layer‐by‐layer approach with nucleic acid and poly(ethylene imine) (PEI), into a variety of mammalian cell lines is studied. In contrast to other studies, the optimal particle diameter for cellular uptake is determined but also the number of therapeutic cargo molecules per cell. It is found that 20 nm AuNPs, with diameters of about 32 nm after the coating process and about 88 nm including the protein corona after incubation in cell culture medium, yield the highest number of nanoparticles and therapeutic DNA molecules per cell. Interestingly, PEI, which is known for its toxicity, can be applied at significantly higher concentrations than its IC₅₀ value, most likely because it is tightly bound to the AuNP surface and/or covered by a protein corona. These results are important for the future design of nanomaterials for the delivery of nucleic acids in two ways. They demonstrate that changes in the nanoparticle size can lead to significant differences in the number of therapeutic molecules delivered per cell, and they reveal that the toxicity of polyelectrolytes can be modulated by an appropriate binding to the nanoparticle surface.     

Self‐Collapsing of Single Molecular Poly‐Propylene Oxide (PPO) in a 3D DNA Network

On the basis of DNA self‐assembly, a thermal responsive polymer polypropylene oxide (PPO) is evenly inserted into a rigid 3D DNA network for the study of single molecular self‐collapsing process. At low temperature, PPO is hydrophilic and dispersed uniformly in the network; when elevating temperature, PPO becomes hydrophobic but can only collapse on itself because of the fixation and separation of DNA rigid network. The process has been characterized by rheological test and Small Angle X‐Ray Scattering test. It is also demonstrated that this self‐collapsing process is reversible and it is believed that this strategy could provide a new tool to study the nucleation‐growing process of block copolymers.     

DNA Hairpin Stabilization on a Hydrophobic Surface

DNA hybridization in the vicinity of surfaces is a fundamental process for self‐assembled nanoarrays, nanocrystal superlattices, and biosensors. It is widely recognized that solid surfaces alter molecular forces governing hybridization relative to a bulk solution, and these effects can either favor or disfavor the hybridized state depending on the specific sequence and surface. Results presented here provide new insights into the dynamics of DNA hairpin‐coil conformational transitions in the vicinity of hydrophilic oligo(ethylene glycol) (OEG) and hydrophobic trimethylsilane (TMS) surfaces. Single‐molecule methods are used to observe the forward and reverse hybridization hairpin‐coil transition of adsorbed species while simultaneously measuring molecular surface diffusion in order to gain insight into surface interactions with individual DNA bases. At least 35 000 individual molecular trajectories are observed on each type of surface. It is found that unfolding slows and the folding rate increases on TMS relative to OEG, despite stronger attractions between TMS and unpaired nucleobases. These rate differences lead to near‐complete hairpin formation on hydrophobic TMS and significant unfolding on hydrophilic OEG, resulting in the surprising conclusion that hydrophobic surface coatings are preferable for nanotechnology applications that rely on DNA hybridization near surfaces.     

An Investigation of PS‐b‐PEO Polymersomes for the Oral Treatment and Diagnosis of Hyperammonemia

Ammonia‐scavenging transmembrane pH‐gradient poly(styrene)‐b‐poly(ethylene oxide) polymersomes are investigated for the oral treatment and diagnosis of hyperammonemia, a condition associated with serious neurologic complications in patients with liver disease as well as in infants with urea cycle disorders. While these polymersomes are highly stable in simulated intestinal fluids at extreme bile salt and osmolality conditions, they unexpectedly do not reduce plasmatic ammonia levels in cirrhotic rats after oral dosing. Incubation in dietary fiber hydrogels mimicking the colonic environment suggests that the vesicles are probably destabilized during the dehydration of the intestinal chyme. The findings question the relevance of commonly used simulated intestinal fluids for studying vesicular stability. With the encapsulation of a pH‐sensitive dye in the polymersome core, the local pH increase upon ammonia influx could be exploited to assess the ammonia concentration in the plasma of healthy and cirrhotic rats as well as in other fluids. Due to its high sensitivity and selectivity, this polymersome‐based assay could prove useful in the monitoring of hyperammonemic patients and in other applications such as drug screening tests.     

Flexible and Tough Poly(lactic acid) Films for Packaging Applications: Property and Processability Improvement by Effective Reactive Blending

This study demonstrates a practical means to overcome inherent brittleness problem of poly(lactic acid) (PLA) and make PLA feasible as packaging material. PLA with suitable processability is utterly required for package manufacturers, where flexible, tough PLA film is essential for packers and end users. Highly flexible PLA films with 60‐fold increase in elongation at break (Eb) over that of the neat PLA were successfully produced by integrating effective reactive blending and economical film blowing process. The ‘two‐step’ blending was used to prepare PLA compound; poly(butylene adipate‐co‐terephthalate) (PBAT – another biodegradable polymer) was first blended with 0.5–1% chain extender (epoxy‐functionalized styrene acrylic copolymer) (ESA), followed by subsequent blending with PLA in twin‐screw extruder. Blown films of reactive blend of PLA/PBAT/ESA (80/20/1) showed impressively high Eb of 250% versus a very low Eb of 4% for the neat PLA. Resulting blown films still possessed high modulus of 2 GPa, yield stress of 50–60 MPa and good toughness of ~100 MPa. Significant enhancement in the film's ductility was attributed to homogeneous blend with developed fine strand‐like structure as a result of effective in situ compatibilization and good interfacial adhesion between the PLA and PBAT. PLA/PBAT/ESA blend also offered improved processability. Resulting films had acceptable haze of ~10% for common packaging, and clearer film close to PLA (≤2%) could be obtained by designing PLA skin layers in multilayer structure. Films of PLA/PBAT/1%ESA exhibit potential as packaging material; their mechanical and optical properties are comparable with or even exceed some existing films used in the market. Copyright © 2015 John Wiley & Sons, Ltd.     

Ultrahigh‐Conductivity Polymer Hydrogels with Arbitrary Structures

A poly(3,4‐ethylenedioxythiophene):poly(4‐styrenesulfonate) (PEDOT:PSS) hydrogel is prepared by thermal treatment of a commercial PEDOT:PSS (PH1000) suspension in 0.1 mol L^?1 sulfuric acid followed by partially removing its PSS component with concentrated sulfuric acid. This hydrogel has a low solid content of 4% (by weight) and an extremely high conductivity of 880 S m^?1. It can be fabricated into different shapes such as films, fibers, and columns with arbitrary sizes for practical applications. A highly conductive and mechanically strong porous fiber is prepared by drying PEDOT:PSS hydrogel fiber to fabricate a current‐collector‐free solid‐state flexible supercapacitor. This fiber supercapacitor delivers a volumetric capacitance as high as 202 F cm^?3 at 0.54 A cm^?3 with an extraordinary high‐rate performance. It also shows excellent electrochemical stability and high flexibility, promising for the application as wearable energy‐storage devices.     

Practical Approach in Developing Desirable Peel–Seal and Clear Lidding Films Based on Poly(Lactic Acid) and Poly(Butylene Adipate‐Co‐Terephthalate) Blends

In this research, poly(lactic acid) (PLA) blend with poly(butylene adipate‐co‐terephthalate) (PBAT) were selected to fabricate peelable lidding films. In general, blending PLA with PBAT results in hazy films; however, desirable low haze films (<10%) could be achieved in this study by designing proper blend composition and cast film process under optimum conditions. Based on various blends containing PBAT ranging from 15 to 30% by weight, it could be seen that a PBAT/PLA blend of 20/80 showed desired optical and peel–seal property, which had a haze of <10% and low peel strength in an easy‐peel characteristic. It was also observed that not only the blend composition but also the film thickness could influence both optical and peel–seal behaviours because the bulk morphology and surface irregularities of the films could vary by changing films' thicknesses. Thus, cast extruded pristine and PBAT/PLA (20/80) blend films of three different thicknesses (20, 35 and 50 μm) were studied. Peel–seal behaviour and optical properties of these films were examined. An I‐peel test (180°) of films sealed on PLA sheet (thickness of ~350 μm) with different interfacial sealing temperature illustrated failure mechanism of four types, i.e. tearing, partial tearing, cohesive and adhesive failure. Based on this study, the PBAT/PLA of 20/80 wt% films with thickness of 20 μm can be used as easy‐peel lidding film sealed with PLA container. Such PBAT/PLA blend films possess a low haze of ~4% and a low peel strength of 8–10 N/15 mm at a broad range of interfacial sealing temperature of 76–105°C. Copyright © 2017 John Wiley & Sons, Ltd.     

Molecular transport characteristics of poly (ethylene‐co‐vinyl acetate) membranes in the presence of normal alkanes

Solvent transport into poly (ethylene‐co‐vinyl acetate) membranes exposed to n‐alkanes has been studied in the temperature interval of 30–60°C. Pure and cross‐linked membranes were prepared. Membranes with different loading of cross‐linking agent were also prepared. It was found that for all liquids, the equilibrium penetrant uptake was influenced by the introduction of cross links. The mechanism of transport has been found to deviate from the regular Fickian behaviour. Transport parameters such as diffusion coefficient, sorption constant and permeability coefficient have been calculated. The influence of temperature on transport was analysed. Transport parameters and activation parameters for the process of diffusion have been calculated. The transport coefficients and the activation parameters showed a dependence on cross‐link density. The Van't Hoff's relationship was used to compute the entropy change. The values of polymer–solvent interaction parameters have been used to calculate the molar mass between cross links of the network polymer. The phantom and affine models were used to analyse the deformation of the networks during swelling. A correlation between theoretical and experimental results was also done. Copyright © 2007 John Wiley & Sons, Ltd.     

Nanoscale DNA tetrahedra improve biomolecular recognition on patterned surfaces

The bottom-up approach of DNA nano-biotechnology can create biomaterials with defined properties relevant for a wide range of applications. This report describes nanoscale DNA tetrahedra that are beneficial to the field of biosensing and the targeted immobilization of biochemical receptors on substrate surfaces. The DNA nanostructures act as immobilization agents that are able to present individual molecules at a defined nanoscale distance to the solvent thereby improving biomolecular recognition of analytes. The tetrahedral display devices are self-assembled from four oligonucleotides. Three of the four tetrahedron vertices are equipped with disulfide groups to enable oriented binding to gold surfaces. The fourth vertex at the top of the bound tetrahedron presents the biomolecular receptor to the solvent. In assays testing the molecular accessibility via DNA hybridization and protein capturing, tetrahedron-tethered receptors outperformed conventional immobilization approaches with regard to specificity and amount of captured polypeptide by a factor of up to seven. The bottom-up strategy of creating DNA tetrahedrons is also compatible with the top-down route of nanopatterning of inorganic substrates, as demonstrated by the specific coating of micro- to nanoscale gold squares amid surrounding blank or poly(ethylene glycol)-passivated glass surfaces. DNA tetrahedra can create biofunctionalized surfaces of rationally designed properties that are of relevance in analytical chemistry, cell biology, and single-molecule biophysics.     

Photoinduced Self‐Assembled Nanostructures and Permanent Polaron Formation in Regioregular Poly(3‐hexylthiophene)

Solution processing of conjugated polymers into ordered self‐assembled precursors has attracted great interest in the past years owing to the ability to manipulate their structural and physical properties. Regioregular poly(3‐hexylthiophene) (P3HT) has become the benchmark polymer in this scenario, where ordered lamellar structures significantly improve carrier mobility of the thin films due to increased crystallinity, extended intrachain conjugation, and ordered interchain π‐stacking. Here, a new photoinduced approach is presented for the generation of highly ordered P3HT aggregate structures that is amenable to the use of visible light to control the aggregate formation. Strong intra‐ and interchain interactions in the solution precursors allow for permanent formation of localized and delocalized polarons that are stable for months. Spin‐coated thin films are found to preserve, in part, the morphological and physical properties of the aggregated P3HT solution precursors with high degree of crystallinity and short π‐stack interchain distances.     

Photosensitive Nanoparticles Combining Vascular‐Independent Intratumor Distribution and On‐Demand Oxygen‐Depot Delivery for Enhanced Cancer Photodynamic Therapy

In drug delivery, the poor tumor perfusion results in disappointing therapeutic efficacy. Nanomedicines for photodynamic therapy (PDT) greatly need deep tumor penetration due to short lifespan and weak diffusion of the cytotoxic reactive oxygen species (ROS). The damage of only shallow cells can easily cause invasiveness and metastasis. Moreover, even if the nanomedicines enter into deeper lesion, the effectiveness of PDT is limited due to the hypoxic microenvironment. Here, a deep penetrating and oxygen self‐sufficient PDT nanoparticle is developed for balanced ROS distribution within tumor and efficient cancer therapy. The designed nanoparticles (CNPs/IP) are doubly emulsified (W/O/W) from poly(ethylene glycol)‐poly(ε‐caprolactone) copolymers doped with photosensitizer IR780 in the O layer and oxygen depot perfluorooctyl bromide (PFOB) inside the core, and functionalized with the tumor penetrating peptide Cys‐Arg‐Gly‐Asp‐Lys (CRGDK). The CRGDK modification significantly improves penetration depth of CNPs/IP and makes the CNPs/IP arrive at both the periphery and hypoxic interior of tumors where the PFOB releases oxygen, effectively alleviating hypoxia and guaranteeing efficient PDT performance. The improved intratumoral distribution of photosensitizer and adequate oxygen supply augment the sensitivity of tumor cells to PDT and significantly improve PDT efficiency. Such a nanosystem provides a potential platform for improved therapeutic index in anticancer therapy.