The use of nanocarriers in biology and medicine is complicated by the current need to understand how nanoparticles interact in complex biological surroundings. When nanocarriers come into contact ...with serum, proteins immediately adsorb onto their surface, forming a protein corona which defines their biological identity. Although the composition of the protein corona has been widely determined by proteomics, its morphology still remains unclear. In this study we show for the first time the morphology of the protein corona using transmission electron microscopy. We are able to demonstrate that the protein corona is not, as commonly supposed, a dense, layered shell coating the nanoparticle, but an undefined, loose network of proteins. Additionally, we are now able to visualize and discriminate between the soft and hard corona using centrifugation-based separation techniques together with proteomic characterization. The protein composition of the ∼15 nm hard corona strongly depends on the surface chemistry of the respective nanomaterial, thus further affecting cellular uptake and intracellular trafficking. Large diameter protein corona resulting from pre-incubation with soft corona or Apo-A1 inhibits cellular uptake, confirming the stealth-effect mechanism. In summary, the knowledge on protein corona formation, composition and morphology is essential to design therapeutic effective nanoparticle systems.
Conjugated polymers have chemically tuneable opto-electronic properties and are easily processed, making them attractive materials for photonics applications. Conjugated polymer lasers, in a variety ...of resonator geometries such as microcavity, micro-ring, distributed feedback and photonic bandgap structures, have been fabricated using a range of coating and imprinting techniques. Currently, one-dimensional nanowires are emerging as promising candidates for integrated, subwavelength active and passive photonic devices. We report the first observation of optically pumped lasing in single conjugated polymer nanowires. The waveguide and resonator properties of each wire are characterized in the far optical field at room temperature. The end faces of the nanowire are optically flat and the nanowire acts as a cylindrical optical cavity, exhibiting axial Fabry-Pérot mode structure in the emission spectrum. Above a threshold incident pump energy, the emission spectrum collapses to a single, sharp peak with an instrument-limited line width that is characteristic of single-mode excitonic laser action.
Formation of the biomolecular corona ultimately determines the successful application of nanoparticles in vivo. Adsorption of biomolecules such as proteins is an inevitable process that takes place ...instantaneously upon contact with physiological fluid (e.g. blood). Therefore, strategies are needed to control this process in order to improve the properties of the nanoparticles and to allow targeted drug delivery. Here, we show that the design of the protein corona by a pre-formed protein corona with tailored properties enables targeted cellular interactions. Nanoparticles were pre-coated with immunoglobulin depleted plasma to create and design a protein corona that reduces cellular uptake by immune cells. It was proven that a pre-formed protein corona remains stable even after nanoparticles were re-introduced to plasma. This opens up the great potential to exploit protein corona formation, which will significantly influence the development of novel nanomaterials.
Polymer transistors are being intensively developed for next-generation flexible electronics. Blends comprising a small amount of semiconducting polymer mixed into an insulating polymer matrix have ...simultaneously shown superior performance and environmental stability in organic field-effect transistors compared with the neat semiconductor. Here we show that such blends actually perform very poorly in the undoped state, and that mobility and on/off ratio are improved dramatically upon moderate doping. Structural investigations show that these blend layers feature nanometre-scale semiconductor domains and a vertical composition gradient. This particular morphology enables a quasi three-dimensional spatial distribution of semiconductor pathways within the insulating matrix, in which charge accumulation and depletion via a gate bias is substantially different from neat semiconductor, and where high on-current and low off-current are simultaneously realized in the stable doped state. Adding only 5 wt% of a semiconducting polymer to a polystyrene matrix, we realized an environmentally stable inverter with gain up to 60.
Perovskite-sensitized solar cells have reached power conversion efficiencies comparable to commercially available solar cells used for example in solar farms. In contrast to silicon solar cells, ...perovskite-sensitized solar cells can be made by solution processes from inexpensive materials. The power conversion efficiency of these cells depends substantially on the charge transfer at interfaces. Here we use Kelvin probe force microscopy to study the real-space cross-sectional distribution of the internal potential within high efficiency mesoscopic methylammonium lead tri-iodide solar cells. We show that the electric field is homogeneous through these devices, similar to that of a p-i-n type junction. On illumination under short-circuit conditions, holes accumulate in front of the hole-transport layer as a consequence of unbalanced charge transport in the device. After light illumination, we find that trapped charges remain inside the active device layers. Removing these traps and the unbalanced charge injection could enable further improvements in performance of perovskite-sensitized solar cells.
Synthetic assembly within living cells represents an innovative way to explore purely chemical tools that can direct and control cellular behavior. We use a simple and modular platform that is ...broadly accessible and yet incorporates highly intricate molecular recognition, immolative, and rearrangement chemistry. Short bimodular peptide sequences undergo a programmed sequence of events that can be tailored within the living intracellular environment. Each sequential stage of the pathways beginning with the cellular uptake, intracellular transport, and localization imposes distinct structural changes that result in the assembly of fibrillar architectures inside cells. The observation of apoptosis, which is characterized by the binding of Annexin V, demonstrates that programmed cell death can be promoted by the peptide assembly. Higher complexity of the assemblies was also achieved by coassembly of two different sequences, resulting in intrinsically fluorescent architectures. As such, we demonstrate that the in situ construction of architectures within cells will broaden the community’s perspective toward how structure formation can impact a living system.
Opacification through calcification of hydrophilic acrylic intraocular lenses (IOL) is a severe complication after cataract surgery. Causing symptoms that range from glare through to severe vision ...loss, the only effective therapy is explantation of the opacified IOL so far. Although IOL calcification is a well-described phenomenon, its pathogenesis is not fully understood yet. The purpose of the current study was to develop a laboratory model to replicate IOL calcification. Calcification could be reproduced using a horizontal electrophoresis and aqueous solutions of calcium chloride and disodium hydrogen phosphate. The analysis of the in vitro calcified IOLs was performed using light microscopy, Alizarin Red and Von Kossa staining, scanning electron microscopy, energy dispersive x-ray spectroscopy and electron crystallography using transmission electron microscopy and electron diffraction. The presented laboratory model could be used to identify hydrophilic IOLs that are at risk to develop calcification and to assess the influence of associated risk factors. In addition, it can serve as a research tool to further understand this pathology.
Abstract
The creation of synthetic polymer nanoobjects with well-defined hierarchical structures is important for a wide range of applications such as nanomaterial synthesis, catalysis, and ...therapeutics. Inspired by the programmability and precise three-dimensional architectures of biomolecules, here we demonstrate the strategy of fabricating controlled hierarchical structures through self-assembly of folded synthetic polymers. Linear poly(2-hydroxyethyl methacrylate) of different lengths are folded into cyclic polymers and their self-assembly into hierarchical structures is elucidated by various experimental techniques and molecular dynamics simulations. Based on their structural similarity, macrocyclic brush polymers with amphiphilic block side chains are synthesized, which can self-assemble into wormlike and higher-ordered structures. Our work points out the vital role of polymer folding in macromolecular self-assembly and establishes a versatile approach for constructing biomimetic hierarchical assemblies.
Attaching targeting ligands on the surface of self-assembled drug delivery systems is the key request for a controlled transport of the drug to a desired location. Most commonly, the amphiphilic ...molecules (block-copolymers, lipids
etc
.) are therefore pre-functionalized before the self-assembly takes place. However, this strategy cannot be applied, if it interferes with the self-assembly process, if the introduced functional groups react with loaded cargo or if natural carriers like extracellular vesicles should be functionalized. Here, we present the site-specific coupling of antibodies to the surface of amino group-terminated liposomes
via
bio-orthogonal copper-free click chemistry after liposome formation. The present primary amino groups were functionalized with a linker carrying a strained alkyne group for a bio-orthogonal strain-promoted alkyne-azide cycloaddition (SPAAC) reaction where Cu(
i
) as a catalyst can be avoided. Antibodies were site-specifically functionalized with azide moieties along the Fc region to avoid interference with the antigen binding sites. The liposome surface functionalization reaction was optimized by precisely analyzing the number of available functional groups (both amine and alkyne), which often represents a challenge for self-assembled systems. By finally confirming the successful antibody coupling, we provide a facile and robust functionalization strategy, which can be applied to a wide range of self-assembled systems and desired targeting antibodies maintaining physiological conditions throughout the procedure.
Attaching targeting ligands on the surface of self-assembled drug delivery systems is one of the key requests for a controlled transport of the drug to a desired location.
The synthesis of hybrid hydrogels by pH‐controlled structural transition with exceptional rheological properties as cellular matrix is reported. “Depsi” peptide sequences are grafted onto a ...polypeptide backbone that undergo a pH‐induced intramolecular O–N–acyl migration at physiological conditions affording peptide nanofibers (PNFs) as supramolecular gelators. The polypeptide–PNF hydrogels are mechanically remarkably robust. They reveal exciting thixotropic behavior with immediate in situ recovery after exposure to various high strains over long periods and self‐repair of defects by instantaneous reassembly. High cytocompatibility, convenient functionalization by coassembly, and controlled enzymatic degradation but stability in 2D and 3D cell culture as demonstrated by the encapsulation of primary human umbilical vein endothelial cells and neuronal cells open many attractive opportunities for 3D tissue engineering and other biomedical applications.
Tissue engineering requires biocompatible, dynamic materials mimicking the extracellular matrix. Hybrid hydrogels from albumin‐derived copolymers grafted with functional peptide nanofiber gelators are developed. pH‐induced intramolecular rearrangement of peptide grafts facilitates gelation at physiological conditions, providing injectability and excellent biocompatibility for primary cells. The mechanically robust hybrids feature ultrafast autonomous self‐recovery and show promise in biomedical applications.
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