Markus J. Barthel

Plasmonic Copper Sulfide Nanocrystals Exhibiting Near-Infrared Photothermal and Photodynamic Therapeutic Effects

Recently, plasmonic copper sulfide (Cu2-xS) nanocrystals (NCs) have attracted much attention as materials for photothermal therapy (PTT). Previous reports have correlated photoinduced cell death to the photothermal heat mechanism of these NCs, and no evidence of their photodynamic properties has been reported yet. Herein we have prepared physiologically stable near-infrared (NIR) plasmonic copper sulfide NCs and analyzed their photothermal and photodynamic properties, including therapeutic potential in cultured melanoma cells and a murine melanoma model. Interestingly, we observe that, besides a high PTT efficacy, these copper sulfide NCs additionally possess intrinsic NIR induced photodynamic activity, whereupon they generate high levels of reactive oxygen species. Furthermore, in vitro and in vivo acute toxic responses of copper sulfide NCs were also elicited. This study highlights a mechanism of NIR light induced cancer therapy, which could pave the way toward more effective nanotherapeutics.

Poly(ethylene oxide) (PEO)-based ABC triblock terpolymers – synthetic complexity vs. application benefits

During the last few decades considerable scientific effort has been devoted to the synthesis, self-assembly, and application of ABC triblock terpolymers with various building blocks. Such materials show high potential in the fields of materials science and life sciences. In particular, poly(ethylene oxide) (PEO) is a versatile building block and related materials featuring PEO segments are often exploited due to its solubility in a wide range of solvents, its non-toxicity, biocompatibility, and the so called “stealth effect”. This review presents a short summary of possible synthetic routes for the synthesis of PEO-containing triblock terpolymers, as well as different applications in the bulk and in solution – including the preparation of porous materials, hybrid systems, and carriers for controlled drug delivery.

Synthesis of Highly Fluorescent Copper Clusters Using Living Polymer Chains as Combined Reducing Agents and Ligands

We present the synthesis of colloidally stable ultrasmall (diameter of 1.5 ± 0.6 nm) and fluorescent copper clusters (Cu-clusters) exhibiting outstanding quantum efficiencies (up to 67% in THF and approximately 30% in water). For this purpose, an amphiphilic block copolymer poly(ethylene glycol)-block-poly(propylene sulfide) (MPEG-b-PPS) was synthesized by living anionic ring-opening polymerization. When CuBr is mixed with the living polymer chains in THF, the formation of Cu-clusters is detected by the appearance of the fluorescence. The cluster growth is quenched by the addition of water, followed by THF removal. The structural features of the MPEG-b-PPS copolymer control the cluster formation and the stabilization: the poly(propylene sulfide) segment acts as coordinating and reducing agent for the copper ions in THF, and imparts a hydrophobic character. This hydrophobic block protects the Cu-clusters from water exposure, thus allowing to obtain a stable emission in water. The PEG segment instead provides the hydrophilicity, rendering the Cu-clusters water-soluble. To obtain fluorescent and stable Cu-clusters exhibiting outstanding quantum efficiencies, the removal of the excess of free polymer and copper salt was crucial. The Cu-clusters are also colloidally and optically stable in physiological media and showed bright fluorescence even when taken up by HeLa cells, being noncytotoxic when administered at a Cu dose between 10 nM and 1.6 μM. Given the very small size of the Cu-clusters, localization and fluorescent staining of cell nucleus is achieved, as demonstrated by confocal cell imaging performed at different Cu-cluster doses and at different incubation temperatures.

Understanding and tuning the self-assembly of polyether-based triblock terpolymers in aqueous solution

The synthesis and self-assembly of well-defined poly(ethylene oxide)-block-poly(allyl glycidyl ether)-block-poly(tert-butyl glycidyl ether) (PEO-b-PAGE-b-PtBGE) triblock terpolymers with varying block lengths of PAGE and PtBGE are reported. The materials were synthesized using sequential living anionic ring-opening polymerization (AROP). The middle block, PAGE, was further modified by post-polymerization addition of 2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactopyranose via thiol–ene chemistry, resulting in PEO-b-PAGEGal-b-PtBGE. Self-assembly of the terpolymers in aqueous media resulted in the predominant formation of core–shell–corona architectures and the aggregates featured a PtBGE core, a PAGE shell, and a PEO corona. The structures were investigated using dynamic light scattering (DLS) and cryogenic transmission electron microscopy (cryo-TEM) measurements. In addition, the presence of a PEO corona rendered the formed micellar structures thermo-responsive, as demonstrated using turbidimetry. Depending on the ratio of hydrophilic to hydrophobic segments and on the thermal history of the samples, several micellar morphologies could be identified, including spheres of different size, worm-like structures, and vesicles. More important, both reversible and irreversible structural rearrangements could be identified during the heating–cooling cycles.

Zwitterionic Nanofibers of Super-Glue for Transparent and Biocompatible Multi-Purpose Coatings

Here we show that macrozwitterions of poly(ethyl 2-cyanoacrylate), commonly called Super Glue, can easily assemble into long and well defined fibers by electrospinning. The resulting fibrous networks are thermally treated on glass in order to create transparent coatings whose superficial morphology recalls the organization of the initial electrospun mats. These textured coatings are characterized by low liquid adhesion and anti-staining performance. Furthermore, the low friction coefficient and excellent scratch resistance make them attractive as solid lubricants. The inherent texture of the coatings positively affects their biocompatibility. In fact, they are able to promote the proliferation and differentiation of myoblast stem cells. Optically-transparent and biocompatible coatings that simultaneously possess characteristics of low water contact angle hysteresis, low friction and mechanical robustness can find application in a wide range of technological sectors, from the construction and automotive industries to electronic and biomedical devices.

Solution self-assembly of poly(ethylene oxide)-block-poly(furfuryl glycidyl ether)-block-poly(allyl glycidyl ether) based triblock terpolymers: a field-flow fractionation study

A well-defined ABC triblock terpolymer, poly(ethylene oxide)-block-poly(furfuryl glycidyl ether)-block-poly(allyl glycidyl ether) (PEO-b-PFGE-b-PAGE), was synthesized via sequential living anionic ring-opening polymerization, and subsequently functionalized by thiol–ene click chemistry. In that way, either a fluorocarbon chain or carboxy groups were introduced into the C segment (PAGE). The self-assembly of the resulting materials in water as selective solvent was studied in detail by asymmetric flow field-flow fractionation (AF4) coupled to multi-angle laser light scattering and dynamic light scattering (DLS). The obtained results were compared with batch DLS and cryogenic transmission electron microscopy (cryo-TEM) results. The influence of the separation conditions on the retention behavior of the triblock terpolymers was evaluated to reveal possible limitations associated with AF4 measurements. The influence of pH value and ionic strength on the solution behavior of the materials, in particular for PEO-b-PFGE-b-PAGECOOH, was investigated as well. Crosslinking of the PAGECOOH by chelating metal ions (Fe3+) was studied under different conditions. In case of PEO-b-PFGE-b-PAGE, spherical micelles of approximately 20 nm (Rh) were observed, whereas the introduction of a fluorocarbon chain led to an increase in size (30 nm, Rh) and the formation of worm-like structures. Carboxy functionalization rendered small (5 nm) disk-like structures. In the latter case, subsequent addition of FeCl3 resulted in the formation of spherical nanostructures ranging from 10 to 60 nm in size, depending on the pH value and the polymer/metal ion ratio.

Amphiphilic polyether-based block copolymers as crosslinkable ligands for Au-nanoparticles

We report on the synthesis of thiol-terminated, polyether-based amphiphilic block copolymers with a hydrophilic poly(ethylene oxide) (PEO) segment and a second crosslinkable block of either poly(furfuryl glycidyl ether) (PFGE) or poly(allyl glycidyl ether) (PAGE). Both block copolymers could be synthesized with narrow dispersities (Đ ≤ 1.07) via living anionic ring-opening polymerization (AROP). Introduction of the thiol-moiety enables the application of these block copolymers as ligands for the preparation of Au-nanoparticles (Au-NPs) by direct reduction of suitable precursors in N,N-dimethylacetamide (DMAc). The ligands of the obtained hybrid nanoparticles featuring an Au core and a block copolymer shell were crosslinked either via Diels–Alder reactions for the PFGE segment or via hydrosilylation chemistry targeting the PAGE segment. In this way, shell-crosslinked Au-NPs with enhanced stability against ligand exchange reactions in the presence of competitive ligands like alkyl thiols could be prepared.

Small but powerful: co-assembly of polyether-based triblock terpolymers into sub-30 nm micelles and synergistic effects on cellular interactions.

We introduce a versatile ABC triblock terpoly- mer platform based on poly(ethylene oxide)-block-poly(allyl glycidyl ether)-block-poly(tert-butyl glycidyl ether) (PEO-b-PAGE-b-PtBGE) and subsequent functionalization of the PAGE segment with thiogalactose (hydroxyl), cysteamine (amino), and 2-mercaptopropionic acid (carboxy) by thiol-ene chemistry. These materials are used to prepare core-shell-corona micelles with a PtBGE core, a PAGE shell, and a PEO corona and sizes below 30 nm in aqueous media. We investigate the influence of different functional groups on micelle formation and cellular uptake. Moreover, co-assembly of differently functionalized materials allows to create micelles with a mixed shell and adjustable charge and, in that way, important characteristics such as cell uptake or cytotoxicity can be controlled. Furthermore, we demonstrate that even the uptake mechanism depends on the substitution pattern of the underlying triblock terpolymer.

Poly(2‐vinyl pyridine)‐block‐Poly(ethylene oxide) Featuring a Furan Group at the Block Junction—Synthesis and Functionalization

Furfuryl glycidyl ether (FGE) represents a highly versatile monomer for the preparation of reversibly cross-linkable nanostructured materials via Diels-Alder reactions. Here, the use of FGE for the mid-chain functionalization of a P2VP-b-PEO diblock copolymer is reported. The material features one furan moiety at the block junction, P2VP68 -FGE-b-PEO390 , which can be subsequently addressed in Diels-Alder reactions using maleimide-functionalized counterparts. The presence of the FGE moiety enables the introduction of dyes as model labels or the formation of hetero-grafted brushes as shell on hybrid Au@Polymer nanoparticles. This renders P2VP68 -FGE-b-PEO390 , a powerful tool for selective functionalization reactions, including the modification of surfaces.

Facile transformation of FeO/Fe3O4 core-shell nanocubes to Fe3O4 via magnetic stimulation.

Here, we propose the use of magnetic hyperthermia as a means to trigger the oxidation of Fe1−xO/Fe3−δO4 core-shell nanocubes to Fe3−δO4 phase. As a first relevant consequence, the specific absorption rate (SAR) of the initial core-shell nanocubes doubles after exposure to 25 cycles of alternating magnetic field stimulation. The improved SAR value was attributed to a gradual transformation of the Fe1−xO core to Fe3−δO4, as evidenced by structural analysis including high resolution electron microscopy and Rietveld analysis of X-ray diffraction patterns. The magnetically oxidized nanocubes, having large and coherent Fe3−δO4 domains, reveal high saturation magnetization and behave superparamagnetically at room temperature. In comparison, the treatment of the same starting core-shell nanocubes by commonly used thermal annealing process renders a transformation to γ-Fe2O3. In contrast to other thermal annealing processes, the method here presented has the advantage of promoting the oxidation at a macroscopic temperature below 37 °C. Using this soft oxidation process, we demonstrate that biotin-functionalized core-shell nanocubes can undergo a mild self-oxidation transformation without losing their functional molecular binding activity.