Tobias Rudolph

Star-shaped drug carriers for doxorubicin with POEGMA and POEtOxMA brush-like shells: a structural, physical, and biological comparison.

The synthesis of amphiphilic star-shaped poly(ε-caprolactone)-block-poly(oligo(ethylene glycol)methacrylate)s ([PCL(18)-b-POEGMA](4)) and poly(ε-caprolactone)-block-poly(oligo(2-ethyl-2-oxazoline)methacrylate)s ([PCL(18)-b-POEtOxMA](4)) is presented. Unimolecular behavior in aqueous systems is observed with the tendency to form loose aggregates for both hydrophilic shell types. The comparison of OEGMA and OEtOxMA reveals that the molar mass of the macromonomer in the hydrophilic shell rather than the mere length is the crucial factor to form an efficiently stabilizing hydrophilic shell. A hydrophilic/lipophilic balance of 0.8 is shown to stabilize unimolecular micelles in water. An extensive in vitro biological evaluation shows neither blood nor cytotoxicity. The applicability of the polymers as drug delivery systems was proven by the encapsulation of the anticancer drug doxorubicin, whose cytotoxic effect was retarded in comparison to the free drug.

Amphiphilic star-shaped block copolymers as unimolecular drug delivery systems: investigations using a novel fungicide

Amphiphilic star-shaped poly(e-caprolactone)-block-poly(oligo(ethylene glycol)methacrylate) [PCLa-b-POEGMAb]4 block copolymers with four arms and varying degrees of polymerization for the core (PCL) and the shell (POEGMA) were used to investigate the solution behavior in dilute aqueous solution using a variety of techniques, including fluorescence and UV/Vis spectroscopy, dynamic light scattering, analytical ultracentrifugation, and isothermal titration calorimetry. Particular emphasis has been applied to prove that the systems form unimolecular micelles for different hydrophilic/lipophilic balances of the employed materials. In vitro cytotoxicity and hemocompatibility have further been investigated to probe the suitability of these structures for in vivo applications. A novel fungicide was included into the hydrophobic core in aqueous media to test their potential as drug delivery systems. After loading, the materials have been shown to release the drug and to provoke therewith an inhibition of the growth of different fungal strains.

Poly(thiolactone) homo- and copolymers from maleimide thiolactone: synthesis and functionalization

We describe the synthesis of a thiolactone-functionalized maleimide (MITla), and its (co)polymerization into poly(thiolactone) homo- and copolymers via controlled or free radical polymerization (CRP or FRP) techniques. Homopolymers were synthesized using FRP whereas MITla was copolymerized with styrene and N-iso-propylacrylamide (NIPAAm) via RAFT. In that way, we were able to combine the properties of a maleimide with the possibility to use the thiolactone side chain functionality in subsequent double modification reactions. Thiolactones are susceptible to nucleophilic ring-opening in the presence of primary amines, releasing a thiol moiety that can be used for conjugate addition (nucleophilic thiol–ene) reactions afterwards. We synthesized and characterized copolymers of different compositions, followed by site-specific double modification reactions with a combination of n-butylamine and methyl acrylate.

Hybrid Fe3O4@amino cellulose nanoparticles in organic media – Heterogeneous ligands for atom transfer radical polymerizations

We demonstrate an efficient strategy for the preparation of well-dispersed hybrid particles in organic media via a combination of the solution-based formation of magnetic nanoparticles (MNPs) and subsequent coating with amino celluloses of different degrees of polymerization. The coating process was verified by a combination of light scattering, thermogravimetry, and magnetic techniques. Further, the hybrid particles exhibit an average diameter of roughly 8 nm, as demonstrated by electron microscopy and light scattering. The stability of the so-called MNP@AC(x) hybrid particles (x represents the average degree of polymerization of the amino cellulose) in polar organic solvents such as DMAc was exploited by using the materials as heterogeneous ligands in the atom transfer radical polymerization (ATRP) of styrene. We could show that PS with a near-narrow molecular weight distribution (PDIs<1.3) and low Cu contents (5 ppm) can be prepared. The MNP@AC(x) particles could be separated from the reaction mixture afterwards by an external magnetic field and reused in further polymerizations.

Controlling Aqueous Self‐Assembly Mechanisms by Hydrophobic Interactions

We report an innovative template-assisted synthetic protocol for the selective functionalization of terminal triple bonds in oligophenyleneethynylenes (OPE) by pre-organization in aqueous solution. By this approach, three new OPE-based bolaamphiphiles substituted with hydrophilic poly(2-ethyl-2-oxazoline) (PEtOx) chains of different length have been synthesized. The chain length was observed to strongly influence the aqueous supramolecular polymerization: bolaamphiphiles with longer hydrophilic chains aggregate into spherical nanoparticles in a stepwise fashion, whereas 2D anisotropic platelets are formed cooperatively if shorter PEtOx chains are used. Our results demonstrate that hydrophobic interactions can be strong enough to trigger cooperative effects in aqueous self-assembly processes.

Understanding Toughness in Bioinspired Cellulose Nanofibril/Polymer Nanocomposites.

Cellulose nanofibrils (CNFs) are considered next generation, renewable reinforcements for sustainable, high-performance bioinspired nanocomposites uniting high stiffness, strength and toughness. However, the challenges associated with making well-defined CNF/polymer nanopaper hybrid structures with well-controlled polymer properties have so far hampered to deduce a quantitative picture of the mechanical properties space and deformation mechanisms, and limits the ability to tune and control the mechanical properties by rational design criteria. Here, we discuss detailed insights on how the thermo-mechanical properties of tailor-made copolymers govern the tensile properties in bioinspired CNF/polymer settings, hence at high fractions of reinforcements and under nanoconfinement conditions for the polymers. To this end, we synthesize a series of fully water-soluble and nonionic copolymers, whose glass transition temperatures (Tg) are varied from -60 to 130 °C. We demonstrate that well-defined polymer-coated core/shell nanofibrils form at intermediate stages and that well-defined nanopaper structures with tunable nanostructure arise. The systematic correlation between the thermal transitions in the (co)polymers, as well as its fraction, on the mechanical properties and deformation mechanisms of the nanocomposites is underscored by tensile tests, SEM imaging of fracture surfaces and dynamic mechanical analysis. An optimum toughness is obtained for copolymers with a Tg close to the testing temperature, where the soft phase possesses the best combination of high molecular mobility and cohesive strength. New deformation modes are activated for the toughest compositions. Our study establishes quantitative structure/property relationships in CNF/(co)polymer nanopapers and opens the design space for future, rational molecular engineering using reversible supramolecular bonds or covalent cross-linking.

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.

Synthesis and self-assembly of poly(ferrocenyldimethylsilane)-block-poly(2-alkyl-2-oxazoline) block copolymers

Herein, we demonstrate the synthesis of chain-end functionalized poly(ferrocenyldimethylsilane) (PFDMS) and poly(2-alkyl-2-oxazoline)s (POx) of different molar mass, and the subsequent macromolecular conjugation to organometallic PFDMS-b-POx block copolymers of different composition via copper-catalyzed azide–alkyne cycloaddition (CuAAC). We distinguish between amphiphilic crystalline-coil PFDMS-b-PEtOx (poly(2-ethyl-2-oxazoline)) and potentially double crystalline PFDMS-b-PiPrOx (poly(2-iso-propyl-2-oxazoline)) materials. After characterization of the obtained block copolymers via SEC, NMR, FT-IR and X-ray scattering, the solution behavior in acetone as a non-solvent for PFDMS was investigated. We found various aggregate morphologies with a PFDMS core and a POx corona (sheets, vesicles, rods), depending on the weight fraction of the organometallic PFDMS segment.

Toward Anisotropic Hybrid Materials: Directional Crystallization of Amphiphilic Polyoxazoline-Based Triblock Terpolymers

We present the design and synthesis of a linear ABC triblock terpolymer for the bottom-up synthesis of anisotropic organic/inorganic hybrid materials: polyethylene-block-poly(2-(4-(tert-butoxycarbonyl)amino)butyl-2-oxazoline)-block-poly(2-iso-propyl-2-oxazoline) (PE-b-PBocAmOx-b-PiPrOx). The synthesis was realized via the covalent linkage of azide-functionalized polyethylene and alkyne functionalized poly(2-alkyl-2-oxazoline) (POx)-based diblock copolymers exploiting copper-catalyzed azide-alkyne cycloaddition (CuAAC) chemistry. After purification of the resulting triblock terpolymer, the middle block was deprotected, resulting in a primary amine in the side chain. In the next step, solution self-assembly into core-shell-corona micelles in aqueous solution was investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Subsequent directional crystallization of the corona-forming block, poly(2-iso-propyl-2-oxazoline), led to the formation of anisotropic superstructures as demonstrated by electron microscopy (SEM and TEM). We present hypotheses concerning the aggregation mechanism as well as first promising results regarding the selective loading of individual domains within such anisotropic nanostructures with metal nanoparticles (Au, Fe3O4).

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.