The toxic effect of monodisperse amorphous silica particles studied on an in vitro model of the human air–blood barrier

Topologically Controlled Interpolyelectrolyte Complexes

The complexation of a cylindrical polyelectrolyte−brush−surfactant complex (PMMPSS−C12) and an oppositely, highly charged cylindrical polyelectrolyte−brush (PMMPEI−PEO) in dimethylformamide (DMF) l...

Polymeric Nanoparticles: Polymeric Nanoparticles with Neglectable Protein Corona (Small 18/2020)

Observation of interaction forces by investigation of the influence of eluent additives on the retention behavior of aqueous nanoparticle dispersions in asymmetrical flow field-flow fractionation.

The investigation and subsequent understanding of the interactions of nanomaterials with components of their surrounding media is important to be able to evaluate both potential use cases as well as potential risks for human health and for the environment. To investigate such interactions, asymmetrical flow field-flow fractionation (AF4) is an interesting analytical tool. This statement grounds on the fact that interactions of the analyte with the membrane and with components of the eluent are crucial for the retention behavior of the analyte within the field-flow fractionation (FFF) channel. Therefore, the investigation of the retention behavior provides an insight in the nature of the int…

Complex Formation of DNA with Oppositely Charged Polyelectrolytes of Different Chain Topology:  Cylindrical Brushes and Dendrimers

The complex formation between DNA (pUC19-supercoiled DNA, 2686 base pairs) and some polycations of different chain topologies in aqueous solution was studied by light scattering, gel electrophoresis, and AFM. The investigated polycations comprised cylindrical brush polymers with quaternized poly(vinylpyridine) and polyethylene imine side chains as well as a fifth generation dendrimer thus covering a broad molar mass regime of 3 × 104 g mol-1 < Mw < 1 × 107 g mol-1 and very different chemical charges/molecule, Z+, of 127 < Z+ < 5500. Irrespective of the polycation, the complexes formed in dilute solution exhibited a similar size in terms of the mean square radius of gyration, 〈Rg2〉, i.e., 30…

Development of a triple-culture model of the alveolar-capillary barrier

Dye loading of amphiphilic poly(organosiloxane) nanoparticles.

Tuning the surface of nanoparticles: Impact of poly(2-ethyl-2-oxazoline) on protein adsorption in serum and cellular uptake

Item does not contain fulltext Due to the adsorption of biomolecules, the control of the biodistribution of nanoparticles is still one of the major challenges of nanomedicine. Poly(2-ethyl-2-oxazoline) (PEtOx) for surface modification of nanoparticles is applied and both protein adsorption and cellular uptake of PEtOxylated nanoparticles versus nanoparticles coated with poly(ethylene glycol) (PEG) and non-coated positively and negatively charged nanoparticles are compared. Therefore, fluorescent poly(organosiloxane) nanoparticles of 15 nm radius are synthesized, which are used as a scaffold for surface modification in a grafting onto approach. With multi-angle dynamic light scattering, asym…

Techniques To Control Polymersome Size

Polymersomes as synthetic analogues of liposomes appear frequently in relevant literature as promising candidates for a wide range of different applications including drug delivery, theranostic multitools, and nanoreactors. In particular, as nanotransporters for nanomedical applications in vivo, requirements concerning the reproducible manufacturing and reliable size control are extremely high. This Perspective highlights the importance of size control especially in the context of nanomedicine and gives an overview of the theoretical background of amphiphilic self-assembly leading to different preparation methods, where their feasibility of controlling polymersomes’ size is discussed.

Polymeric Nanoparticles with Neglectable Protein Corona

Small : nano micro 16(18), 1907574 (2020). doi:10.1002/smll.201907574

Cylindrical polyelectrolyte-comb-surfactant complexes

Abstract Quaternized polymer combs based on poly(2-vinylpyridine-macromonomers) and the surfactant sodium dodecylsulfate are employed in the synthesis of a novel cylindrical polyelectrolyte-comb-surfactant complex (PECSC). The complex formed has 1:1 stoichiometry with respect to the ratio of dodecylsulfate to pyridinium units. It is soluble in organic solvents such as 2-butanol or chloroform. Characterization of single particle properties of the complex in organic solution is possible and yields a radius of gyration of 〈Rg〉z = 78.4 nm, a hydrodynamic radius of 〈1/Rh〉z−1 = 51.4 nm and a cross-sectional radius of Rg,cross = 3.9 nm in chloroform. The characteristic ratio γ = 〈Rg〉z/〈1/Rh〉z−1 de…

Viscoelasticity of pore-spanning polymer membranes derived from giant polymersomes

We show how the viscoelastic properties of membranes formed from poly(butadiene)-block-poly(ethylene oxide) (PB130-b-PEO66) block copolymers can be locally accessed by atomic force microscopy. Polymer membranes are spread on microstructured porous silicon substrates from PB130-b-PEO66 vesicles by decreasing the osmotic pressure of the solution. Local viscoelastic properties of the pore-spanning polymer membranes were obtained from site-specific indentation experiments. Elastic moduli of these membranes were in the order of few MPa, while the elastic moduli of cross-linked membranes considerably increased to few GPa. Furthermore, the energy dissipation and velocity dependence of the hysteres…

Inflammatory and cytotoxic responses of an alveolar-capillary coculture model to silica nanoparticles: Comparison with conventional monocultures

Abstract Background To date silica nanoparticles (SNPs) play an important role in modern technology and nanomedicine. SNPs are present in various materials (tyres, electrical and thermal insulation material, photovoltaic facilities). They are also used in products that are directly exposed to humans such as cosmetics or toothpaste. For that reason it is of great concern to evaluate the possible hazards of these engineered particles for human health. Attention should primarily be focussed on SNP effects on biological barriers. Accidentally released SNP could, for example, encounter the alveolar-capillary barrier by inhalation. In this study we examined the inflammatory and cytotoxic response…

Functionalization of Crosslinked Vesicles by Co-Self-Assembly of a Gelable Diblock Copolymer and Mercaptosilane

Herein, a convenient and general method to simultaneously fix and functionalize polymeric vesicles with sulphydryl groups by the co-self-assembly of poly(ethylene oxide)-block-poly[3-(triethoxysilyl)propyl methacrylate] (PEO-b-PTESPMA) and 3-mercaptopropyltrialkoxysilane in an aqueous solution is reported. The presence of sulphydryl groups across the vesicle membrane has been confirmed by using an energy-filtered technique during TEM analysis and by capturing Au nanoparticles.

Flotillin-involved uptake of silica nanoparticles and responses of an alveolar-capillary barrier in vitro

AbstractDrug and gene delivery via nanoparticles across biological barriers such as the alveolar-capillary barrier of the lung constitutes an interesting and increasingly relevant field in nanomedicine. Nevertheless, potential hazardous effects of nanoparticles (NPs) as well as their cellular and systemic fate should be thoroughly examined. Hence, this study was designed to evaluate the effects of amorphous silica NPs (Sicastar) and (poly)organosiloxane NPs (AmOrSil) on the viability and the inflammatory response as well as on the cellular uptake mechanisms and fate in cells of the alveolar barrier. For this purpose, the alveolar epithelial cell line (NCI H441) and microvascular endothelial…

Farbstoffbeladung von amphiphilen Poly(organosiloxan)-Nanopartikeln

Continuously manufactured magnetic polymersomes--a versatile tool (not only) for targeted cancer therapy.

Micromixer technology was used to prepare polymeric vesicles (Pluronic® L-121) dual loaded with the anti-cancer drug camptothecin and magnetic nanoparticles. Successful incorporation of the magnetic nanoparticles was confirmed by transmission electron microscopy. Dynamic light scattering measurements showed a relatively narrow size distribution of the hybrid polymersomes. Camptothecin polymersomes reduced the cell viability of prostate cancer cells (PC-3) measured after 72 h significantly, while drug-free polymersomes showed no cytotoxic effects. Covalent attachment of a cancer targeting peptide (bombesin) as well as a fluorescent label (Alexa Fluor® 647) to the hybrid polymersomes was perf…

Amphiphilic Poly(organosiloxane) Nanospheres as Nanoreactors for the Synthesis of Topologically Trapped Gold, Silver, and Palladium Colloids

Amphiphilic poly(organosiloxane) nanospheres with different core−shell architectures are employed as passive nanoreactors for the synthesis of noble metal colloids. The amphiphilic poly(organosiloxane) nanospheres, which have diameters between 15 and 40 nm, possess a hydrophilic interior and a hydrophobic shell. Dispersed in organic solvents such as toluene, it has been achieved to transfer hydrophilic noble metal salts through the solvent into the nanospheres by either liquid−liquid or solid−liquid phase transfer. Subsequently, reduction of the noble metal salt with lithium triethylborohydride led to the formation of 2−5 nm sized noble metal colloids. If the network density of the shell of…

Double-Shell Vesicles, Strings of Vesicles and Filaments Found in Crosslinked Micellar Solutions of Poly(1,2-butadiene)-block-poly(ethylene oxide) Diblock Copolymers

Micellar structures of amphiphilic poly(1,2-butadiene)-block-poly(ethylene oxide) diblock copolymers have been crosslinked in aqueous solution by γ-irradiation. By transmission electron microscopy (TEM) of neganively stained specimen it is shown that the precominant structures present are sopolymer sesicles (which appear to be double latered. These fived vesules are stable with respect to their share and can be transferred from water into a good solvent for blue filbeks, such as tetrahydrofuran, this demonstrating the effectiveness of the crosslinking. In addition to the resicles a small number of flexible cylindrichl/filimented structures sequentially fused vesicles/strings of vesicles and…

Characterization of Polyorganosiloxane Nanoparticles in Aqueous Dispersion by Asymmetrical Flow Field-Flow Fractionation

The advantages of asymmetrical flow field-flow fractionation (AF-FFF) for the characterization of aqueous dispersions of spherical polyorganosiloxane nanoparticles are discussed. With AF-FFF it was possible to obtain information about the synthesis, which is based on the hydrolysis and condensation of alkylalkoxysilanes in aqueous dispersion, and the average size of the spherical nanoparticles in the complex mixture in the presence of excess surfactant. The results are compared to measurements performed with dynamic light scattering (DLS). The size of the nanoparticles increases as a function of the amount of added monomer. Particles with radii between 2 and 50 nm are observed. If only the …

Nanoparticles Built of Cross-Linked Heterotelechelic, Amphiphilic Poly(dimethylsiloxane)-b-poly(ethylene oxide) Diblock Copolymers

Novel short chain α,ω-heterotelechelic amphiphilic poly(dimethylsiloxane)-b-poly(ethylene oxide) diblock copolymers (PDMS−PEO) with total molecular weights below 10 000 g/mol are synthesized, characterized, and used as basic constituent parts for functionalized nanoparticles. The self-assembly of the amphiphilic diblock copolymer in water as a solvent selective for the PEO block leads to the formation of spherical and cylindrical micellar structures with diameters between 10 and 25 nm. The core of the micelles is built of the hydrophobic PDMS chains, whereas the corona is set up by the hydrophilic PEO blocks. By using α,ω-heterotelechelic diblock copolymers, it is possible to fix the core o…

Water-soluble, cyclodextrin-functionalized semiconductor nanocrystals: Preparation and pH-dependent aggregation and emission properties

Abstract Using peramino-functionalized β-cyclodextrin molecules for phase.transfer of hydrophobic CdSe multishell nanocrystals into water, we obtained hydrophilic nanoparticles with high quantum yield (up to 50%). At pH > 9, the aqueous solution of these nanocrystals remained stable for several months. The nanoparticles showed a strong influence of the pH of the aqueous solution on the emission of the nanocrystals: the quantum yield varied reversible from ∼10% at pH=6 to ∼50% at pH=14, an effect which according to particle size characterization by dynamic light-scattering and asymmetric flow field-flow fractionation has mainly been attributed to reversible partial aggregation of the hydroph…

Structure Formation of Polymeric Building Blocks: Complex Polymer Architectures

This chapter describes macromolecules with a complex structure, their defined aggregation in solution, their adsorption to surfaces, and their possible aggregation on surfaces. The term “complex structure” implies that the macromolecules show different, distinct structural elements or building blocks on a supra-atomic length scale. Key to understanding the complex structure of macromolecules, their aggregation, and adsorption to surfaces are intra- and intermolecular interactions such as van der Waals, electrostatic, π–π interactions, and hydrogen bonds.

Multihydroxyl-Functional Polystyrenes in Continuous Flow

We describe the synthesis of end-functionalized polystyrenes by living anionic polymerization in a microstructured reactor via termination by acetal-protected functional epoxides. Initiation of styrene polymerization by alkyllithium takes place in a micromixing device with efficient heat and mass transfer properties. A newly developed continuous polymerization−termination sequence enabled quantitative functionalization of the living carbanions by nucleophilic displacement with different, specifically designed glycidyl ethers (ethoxy ethyl glycidyl ether (EEGE), 1,2-isopropylidene glyceryl glycidyl ether (IGG), and trans-2-phenyl-1,3-dioxane glycidyl ether (PDGE)). Upon acidic hydrolysis the…

Uptake of polymeric nanoparticles in a human induced pluripotent stem cell-based blood-brain barrier model: Impact of size, material, and protein corona.

The blood–brain barrier (BBB) maintains the homeostasis of the central nervous system, which is one of the reasons for the treatments of brain disorders being challenging in nature. Nanoparticles (NPs) have been seen as potential drug delivery systems to the brain overcoming the tight barrier of endothelial cells. Using a BBB model system based on human induced pluripotent stem cells (iPSCs), the impact of polymeric nanoparticles has been studied in relation to nanoparticle size, material, and protein corona. PLGA [poly(lactic-co-glycolic acid)] and PLLA [poly(d,l-lactide)] nanoparticles stabilized with Tween® 80 were synthesized (50 and 100 nm). iPSCs were differentiated into human brain m…

Nanoparticle Size Is a Critical Physicochemical Determinant of the Human Blood Plasma Corona: A Comprehensive Quantitative Proteomic Analysis

In biological fluids, proteins associate with nanoparticles, leading to a protein "corona" defining the biological identity of the particle. However, a comprehensive knowledge of particle-guided protein fingerprints and their dependence on nanomaterial properties is incomplete. We studied the long-lived ("hard") blood plasma derived corona on monodispersed amorphous silica nanoparticles differing in size (20, 30, and 100 nm). Employing label-free liquid chromatography mass spectrometry, one- and two-dimensional gel electrophoresis, and immunoblotting the composition of the protein corona was analyzed not only qualitatively but also quantitatively. Detected proteins were bioinformatically cl…

Magnetic polyorganosiloxane core–shell nanoparticles: Synthesis, characterization and magnetic fractionation

Abstact Here, we present the synthesis, characterization and magnetic separation of magnetic polyorganosiloxane nanoparticles. Magnetic iron oxide nanoparticles with average particle radii of 3.2 nm had been synthesized by a simple coprecipitation process of iron(II) and iron(III) salt in basic solution. Afterwards, the particles were successfully incorporated into a polyorganosiloxane network via a polycondensation reaction of trimethoxymethylsilane (T), diethoxydimethylsilane (D) and the functional monomer (chloromethylphenyl)trimethoxysilane (ClBz-T) in aqueous dispersion. A core–shell system was chosen to increase the flexibility of the system concerning size, composition and functional…

Investigation of various shellac grades: additional analysis for identity.

Background: A number of different grades of shellac are commercially available and most of them are known only as generic shellac and are not further differentiated. The investigated grades of shellac in this study are based on different insect strains, host trees, refining methods, and products from different suppliers. Method: The Gardner/Iodine color values of alcoholic and aqueous solutions of the various shellac grades were measured. Glass transition temperatures and pKa-values were determined. To assess chemical differences in the tested shellac grades, MALDI-TOF analysis was performed. Results: Differences were found in color, TG, and pKa-values and in the mass spectra by MALDI-TOF a…

Topologically Controlled Inter-Polyelectrolyte Complexes between Molecular Bottlebrushes and Dendrimers

The complexation of a cylindrical polyelectrolyte−brush-surfactant complex (PMMPSS−C12) and an oppositely charged generation-5 PAMAM dendrimer (G5-PAMAM) in methanol (MeOH) leads to kinetically con...

Multifunctional nanocarriers for biomedical applications

Polymeric vesicles (Pluronic ® L-121) loaded with magnetic nanoparticles (MNP) and an anti-cancer drug (camptothecin) were prepared continuously in a micro mixing device. Characterization by TEM confirmed the successful incorporation of the MNP and DLS measurements showed a relatively narrow size distribution of the hybrid polymersomes. A very high drug loading of camptothecin (100 μg/ml in the polymersome formulation) was reached and a drug release study of loaded magnetic polymersomes has shown a sustained camptothecin release over several days. Carboxylation of Pluronic ® L-121 was performed and enabled a further surface functionalization with bombesin, a 14 amino acid peptide, which bin…

Synthesis, characterization and fine-tuning of bimodal poly(organosiloxane) nanoparticles

Abstract The acid catalyzed sol–gel type synthesis of polyorganosiloxane core-shell nanoparticles with removable PDMS core in aqueous dispersion leads to the inherent formation of a bimodal size distribution with smaller spheres having approximately 26 nm radii and larger nanoparticles with 60 nm in radius. The origin of the self-organized bimodality is investigated and finally attributed to a combination of stabilization of the growing particles due to i) a miniemulsion-type stabilization by the ultrahydrophobe PDMS and ii) by surface co-stabilization by the employed surfactant. The significant influence of temperature, pH, stirrer speed and amount of the surfactant on the particle sizes a…

High-resolution investigation of nanoparticle interaction with a model pulmonary surfactant monolayer.

The pulmonary surfactant film spanning the inner alveolar surface prevents alveolar collapse during the end-exhalation and reduces the work of breathing. Nanoparticles (NPs) present in the atmosphere or nanocarriers targeted through the pulmonary route for medical purposes challenge this biological barrier. During interaction with or passage of NPs through the alveolar surfactant, the biophysical functioning of the film may be altered. However, experimental evidence showing detailed biophysical interaction of NPs with the pulmonary surfactant film are scant. In this study, we have investigated the impact of a hydrophobic polyorganosiloxane (AmOrSil20) NPs on the integrity as well as on the …

Application of the negative staining technique to both aqueous and organic solvent solutions of polymer particles

Abstract Transmission electron microscopy (TEM) imaging of several different polymers in aqueous and organic solutions using the negative staining technique is demonstrated, to emphasise the possibilities of this specimen preparation technique for polymer science. Negative stains can readily be prepared in both water and organic solvents (e.g. dimethyl formamide (DMF), dimethyl sulfoxide (DMSO) and tetrahydrofurane (THF)). Polymer particle size, size distribution and shape seen in negative stain correlates well with those of unstained materials. The particle surface and smaller particles (e.g. 10–20 nm) are more clearly defined in the presence of a negative stain. The inherent problems of s…

Polystyrene Sulfonate–Porphyrin Assemblies: Influence of Polyelectrolyte and Porphyrin Structure

In this study, electrostatic self-assembly of different polystyrene sulfonates and a set of tetravalent cationic porphyrins is investigated. It is shown that association of linear polystyrene sulfonates of different molar masses yields finite size nanoscale assemblies that are stable in aqueous solution. Aggregates are compared to the ones of cylindrical brushes, revealing that both form assemblies in the 100 nm range with the charge ratio (molar ratio of porphyrin charges to polyelectrolyte charges) being determining, while the morphology of the resulting network-like assemblies is different for both polyelectrolyte architectures. For the smallest 8k polystyrene sulfonate, in addition, sto…

One-pot synthesis of poly(l-lactide) multi-arm star copolymers based on a polyester polyol macroinitiator

Abstract Using a hyperbranched poly(glycolide) ( hb PGA) macroinitiator the synthesis of poly( l -lactide) (PLLA) multi-arm star polyesters has been achieved via a core-first approach. The star-shaped copolymers were prepared in a one-pot two-step process via Sn(Oct) 2 -catalyzed ring-opening polymerization (ROP) conducted in the melt. Complete conversion of the end groups of the hb polyglycolide polyester polyols is ensured by the reactive primary hydroxyl termini. By adjusting the monomer/initiator ratio a series of star copolymers with varying PLLA arm length has been obtained with molecular weights in the range of 1500 to 10,000 g/mol (SEC). The successful coupling of the PLLA arms to t…

Hockey-Puck micelles from oligo(p-benzamide)-b-PEG rod-coil block copolymers.

Interactions of silica nanoparticles with lung epithelial cells and the association to flotillins

Amorphous silica nanoparticles (aSNPs) gain increasing popularity for industrial and therapeutic claims. The lung with its surface area of 100-140 m(2) displays an ideal target for therapeutic approaches, but it represents also a serious area of attack for harmful nanomaterials. The exact nature of the cytotoxic effects of NPs is still unknown. Furthermore, cellular pathways and the destiny of internalized NPs are still poorly understood. Therefore, we examined the cytotoxicity (MTS, LDH) and inflammatory responses (IL-8) for different-sized aSNPs (30, 70, 300 nm) on our lung epithelial cells line NCI H441 and endothelial cell line ISO-HAS-1. Additionally, colocalization studies have been c…

Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology

In biological fluids, proteins bind to the surface of nanoparticles to form a coating known as the protein corona, which can critically affect the interaction of the nanoparticles with living systems. As physiological systems are highly dynamic, it is important to obtain a time-resolved knowledge of protein-corona formation, development and biological relevancy. Here we show that label-free snapshot proteomics can be used to obtain quantitative time-resolved profiles of human plasma coronas formed on silica and polystyrene nanoparticles of various size and surface functionalization. Complex time- and nanoparticle-specific coronas, which comprise almost 300 different proteins, were found to …

Influence of oscillating main flow on separation efficiency in asymmetrical flow field-flow fractionation.

The steadily rising interest in the investigation of interactions between nanomaterials and biological media has also led to an increasing interest in asymmetrical flow field-flow fractionation (AF-FFF). The biggest strength of AF-FFF is the possibility to alter the flow profiles to suit a specific separation problem. In this paper, the influence of an oscillating main flow on the separation efficiency of AF-FFF is investigated. Such oscillations can e.g. be caused by the main pump To investigate the influence of such flow conditions on the separation efficiency in AF-FFF systematically, different oscillation profiles were applied and their influence on the elution profile and the retention…

Size influences the effect of hydrophobic nanoparticles on lung surfactant model systems

Item does not contain fulltext The alveolar lung surfactant (LS) is a complex lipid protein mixture that forms an interfacial monolayer reducing the surface tension to near zero values and thus preventing the lungs from collapse. Due to the expanding field of nanotechnology and the corresponding unavoidable exposure of human beings from the air, it is crucial to study the potential effects of nanoparticles (NPs) on the structural organization of the lung surfactant system. In the present study, we investigated both, the domain structure in pure DPPC monolayers as well as in lung surfactant model systems. In the pure lipid system we found that two different sized hydrophobic polymeric nanopa…

Magnetic Composite Thin Films of FexOy Nanoparticles and Photocrosslinked Dextran Hydrogels

Abstract Magnetic hydrogel composites are promising candidates for a broad field of applications from medicine to mechanical engineering. Here, surface-attached composite films of magnetic nanoparticles (MNP) and a polymeric hydrogel (HG) were prepared from magnetic iron oxide nanoparticles and a carboxymethylated dextran with photoreactive benzophenone substituents. A blend of the MNP and the dextran polymer was prepared by mixing in solution, and after spin-coating and drying the blend film was converted into a stable MNP–HG composite by photocrosslinking through irradiation with UV light. The bulk composite material shows strong mobility in a magnetic field, imparted by the MNPs. By util…

Vinylic polymerization of norbornene by Pd(II)-catalysis in the presence of ethylene

Pd(II) catalysts with nitrilo ligands and BF4− counter ions give the best results in vinylic polymerization of norbornene. Absolute molecular weight determination of polynorbornene (PN) by means of light scattering and the three-dimensional shape of PN were also investigated. By correlation of molecular weights Mw with intrinsic viscosity (Staudinger-index) [η], yield a close to 0.5 exponent for the Mark-Houwink equation with solvents chlorobenzene and cyclohexane at 25°C expected for polymer molecules with confined conformation. The vinylic polymerization of norbornene with [(CH3CN)4Pd][BF4]2 (I) in nitromethane in the presence of ethylene results in PN with narrow molecular weight distrib…

Hockeypuck-Micellen aus Oligo(p-benzamid)-b-PEG-Stab-Knäuel-Blockcopolymeren