Holger Schmalz

Precise hierarchical self-assembly of multicompartment micelles

Hierarchical self-assembly offers elegant and energy-efficient bottom-up strategies for the structuring of complex materials. For block copolymers, the last decade witnessed great progress in diversifying the structural complexity of solution-based assemblies into multicompartment micelles. However, a general understanding of what governs multicompartment micelle morphologies and polydispersity, and how to manipulate their hierarchical superstructures using straightforward concepts and readily accessible polymers remains unreached. Here we demonstrate how to create homogeneous multicompartment micelles with unprecedented structural control via the intermediate pre-assembly of subunits. This directed self-assembly leads to a step-wise reduction of the degree of conformational freedom and dynamics and avoids undesirable kinetic obstacles during the structure build-up. It yields a general concept for homogeneous populations of well-defined multicompartment micelles with precisely tunable patchiness, while using simple linear ABC triblock terpolymers. We further demonstrate control over the hierarchical step-growth polymerization of multicompartment micelles into micron-scale segmented supracolloidal polymers as an example of programmable mesoscale colloidal hierarchies via well-defined patchy nanoobjects.

Guided hierarchical co-assembly of soft patchy nanoparticles

The concept of hierarchical bottom-up structuring commonly encountered in natural materials provides inspiration for the design of complex artificial materials with advanced functionalities. Natural processes have achieved the orchestration of multicomponent systems across many length scales with very high precision, but man-made self-assemblies still face obstacles in realizing well-defined hierarchical structures. In particle-based self-assembly, the challenge is to program symmetries and periodicities of superstructures by providing monodisperse building blocks with suitable shape anisotropy or anisotropic interaction patterns (‘patches’). Irregularities in particle architecture are intolerable because they generate defects that amplify throughout the hierarchical levels. For patchy microscopic hard colloids, this challenge has been approached by using top-down methods (such as metal shading or microcontact printing), enabling molecule-like directionality during aggregation. However, both top-down procedures and particulate systems based on molecular assembly struggle to fabricate patchy particles controllably in the desired size regime (10–100 nm). Here we introduce the co-assembly of dynamic patchy nanoparticles—that is, soft patchy nanoparticles that are intrinsically self-assembled and monodisperse—as a modular approach for producing well-ordered binary and ternary supracolloidal hierarchical assemblies. We bridge up to three hierarchical levels by guiding triblock terpolymers (length scale ∼10 nm) to form soft patchy nanoparticles (20–50 nm) of different symmetries that, in combination, co-assemble into substructured, compartmentalized materials (>10 μm) with predictable and tunable nanoscale periodicities. We establish how molecular control over polymer composition programs the building block symmetries and regulates particle positioning, offering a route to well-ordered mixed mesostructures of high complexity.

Water-soluble organo-silica hybrid nanowires.

There has been growing interest in the past decade in one-dimensional (1D) nanostructures, such as nanowires, nanotubes or nanorods, owing to their size-dependent optical and electronic properties and their potential application as building blocks, interconnects and functional components for assembling nanodevices. Significant progress has been made; however, the strict control of the distinctive geometry at extremely small size for 1D structures remains a great challenge in this field. The anisotropic nature of cylindrical polymer brushes has been applied to template 1D nanostructured materials, such as metal, semiconductor or magnetic nanowires. Here, by constructing the cylindrical polymer brushes themselves with a precursor-containing monomer, we successfully synthesized hybrid nanowires with a silsesquioxane core and a shell made up from oligo(ethylene glycol) methacrylate units, which are soluble in water and many organic solvents. The length and diameter of these rigid wires are tunable by the degrees of polymerization of both the backbone and the side chain. They show lyotropic liquid-crystalline behaviour and can be pyrolysed to silica nanowires. This approach provides a route to the controlled fabrication of inorganic or hybrid silica nanostructures by living polymerization techniques.

Facile, Solution-Based Synthesis of Soft, Nanoscale Janus Particles with Tunable Janus Balance

We present a novel, versatile, and simple solution-based routine to produce soft, nanosized Janus particles with tunable structural and physical properties at high volume yield. This process is based on the cross-linking of compartments within precisely defined multicompartment micelles (MCMs), which are themselves formed by the self-assembly of ABC triblock terpolymers. Therein, the C blocks form the stabilizing corona emanating from B compartments, which in turn reside on an A core. Cross-linking of the B compartments allows to permanently fixate the phase-separated state and dissolution in a good solvent for all blocks breaks up the MCMs into single Janus particles. They now consist of a core of cross-linked B blocks and two phase-separated hemispheres of A and C. The process gives access to unprecedented structural features such as tunable core diameter and control over the Janus balance ranging from dominant A side to equal hemispheres to dominant C side. We demonstrate that this simple one-pot approach can be extended to a range of triblock terpolymers with different block lengths and block chemistries to furnish a library of tailor-made Janus particles with widely tunable physical properties. Such a diversity and simplicity has remained unreachable with our previously developed approach using the controlled cross-linking of bulk morphologies. We show that this new synthetic route can be upscaled to a high volume yield of 10 wt %, thereby enabling large-scale applications. We further demonstrate the effect of the Janus balance on colloidal self-assembly. Janus particles with a dominant hydrophobic and a small hydrophilic patch aggregate into large clusters in water, but merely di- or trimerize in chloroform.

General pathway toward crystalline-core micelles with tunable morphology and corona segregation.

We present a general mechanism for the solution self-assembly of crystalline-core micelles (CCMs) from triblock copolymers bearing a semicrystalline polyethylene (PE) middle block. This approach enables the production of nanoparticles with tunable dimensions and surface structures. Depending on the quality of the solvent used for PE, either spherical or worm-like CCMs can be generated in an easy and highly selective fashion from the same triblock copolymers via crystallization-induced self-assembly upon cooling. If the triblock copolymer stays molecularly dissolved at temperatures above the crystallization temperature of the PE block, worm-like CCMs with high aspect ratios are formed by a nucleation and growth process. Their length can be conveniently controlled by varying the applied crystallization temperature. If exclusively spherical micelles with an amorphous PE core are present before crystallization, confined crystallization within the cores of the preformed micelles takes place and spherical CCMs are formed. For polystyrene-block-polyethylene-block-poly(methyl methacrylate) triblock terpolymers a patch-like microphase separation of the corona is obtained for both spherical and worm-like CCMs due to the incompatibility of the PS and PMMA blocks. The structure of the patch-like corona depends on the selectivity of the employed solvent for the PS and PMMA corona blocks, whereby nonselective solvents produce a more homogeneous patch size and distribution. Annealing of the semicrystalline PE cores results in an increasingly uniform crystallite size distribution and thus core thickness of the worm-like CCMs.

Interpolyelectrolyte Complexes of Dynamic Multicompartment Micelles

Dynamic core-shell-shell-corona micelles are formed between two oppositely charged block copolymer systems. Preformed polybutadiene-block-poly(N-methyl-2-vinylpyridinium)-block-poly(methacrylic acid) (PB-P2VPq-PMAA) block terpolymer micelles with a soft polybutadiene core, an interpolyelectrolyte complex (IPEC) shell made out of poly(N-methyl-2-vinylpyridinium) and poly(methacrylic acid), and a negatively charged PMAA corona were mixed in different ratios at high pH with positively charged poly(N-methyl-2-vinylpyridinium)-block-poly(ethylene oxide) (P2VPq-PEO) diblock copolymers. Under these conditions, mixing results in the formation of a second IPEC shell onto the PB-P2VPq-PMAA precursor micelles, surrounded by a PEO corona. The resulting multicompartmented IPECs exhibit dynamic behavior, highlighted by a structural relaxation within a period of 10 days, investigated by dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryo-TEM), and scanning force microscopy (SFM). After a short mixing time of 1 h, the IPECs exhibit a star-shaped structure, whereas after 10 days, spherical core-shell-shell-corona objects could be observed. To further increase complexity and versatility of the presented systems, the in situ formation of gold nanoparticles (Au NPs) in both the precursor micelles and the equilibrated IPEC was tested. For the PB-P2VPq-PMAA micelles, NP formation resulted in narrowly distributed Au NPs located within the PMAA shell, whereas for the core-shell-shell-corona IPEC, the Au NPs were confined within the IPEC shell and shielded from the outside through the PEO corona.

Dual-responsive magnetic core-shell nanoparticles for nonviral gene delivery and cell separation.

We present the synthesis of dual-responsive (pH and temperature) magnetic core-shell nanoparticles utilizing the grafting-from approach. First, oleic acid stabilized superparamagnetic maghemite (γ-Fe(2)O(3)) nanoparticles (NPs), prepared by thermal decomposition of iron pentacarbonyl, were surface-functionalized with ATRP initiating sites bearing a dopamine anchor group via ligand exchange. Subsequently, 2-(dimethylamino)ethyl methacrylate (DMAEMA) was polymerized from the surface by ATRP, yielding dual-responsive magnetic core-shell NPs (γ-Fe(2)O(3)@PDMAEMA). The attachment of the dopamine anchor group on the nanoparticles surface is shown to be reversible to a certain extent, resulting in a grafting density of 0.15 chains per nm(2) after purification. Nevertheless, the grafted NPs show excellent long-term stability in water over a wide pH range and exhibit a pH- and temperature-dependent reversible agglomeration, as revealed by turbidimetry. The efficiency of γ-Fe(2)O(3)@PDMAEMA hybrid nanoparticles as a potential transfection agent was explored under standard conditions in CHO-K1 cells. Remarkably, γ-Fe(2)O(3)@PDMAEMA led to a 2-fold increase in the transfection efficiency without increasing the cytotoxicity, as compared to polyethyleneimine (PEI), and yielded on average more than 50% transfected cells. Moreover, after transfection with the hybrid nanoparticles, the cells acquired magnetic properties that could be used for selective isolation of transfected cells.

Magnetic and fluorescent glycopolymer hybrid nanoparticles for intranuclear optical imaging.

The synthesis of galactose-displaying core-shell nanospheres exhibiting both fluorescent and magnetic properties by grafting a glycocopolymer consisting of 6-O-methacryloylgalactopyranose (MAGal) and 4-(pyrenyl)butyl methacrylate (PyMA) onto magnetic silica particles via thiol-ene chemistry is reported. Magnetization measurements indicated that neither the encapsulation of the iron oxide particles into silica nor the grafting of the glycocopolymer chains had a significant influence on the superparamagnetic properties. This not only simplifies the purification of the particles but may facilitate the use of the particles in applications such as hyperthermia or magnetic resonance imaging (MRI). Furthermore, the hydrophilic glycopolymer shell provided solubility of the particles in aqueous medium and enabled the uptake of the particles into the cytoplasm and nucleus of lung cancer cells via carbohydrate-lectin recognition effects.

Crystallization -induced switching of the morphology of poly(ethylene oxide)- block -polybutadiene micelles

We studied the morphology of micelles formed by a well-defined poly(1,2-butadiene)-block-poly(ethylene oxide) diblock copolymer (PB-b-PEO). Dissolved in n-heptane at 70 °C, that is, above the melting point of PEO, spherical micelles are formed due to the selectivity of the solvent for the PB-block. If the solutions are cooled down to low temperatures, the liquid PEO-block crystallizes within the cores of the spherical micelles that remain stable. If, however, the solutions are quenched to 30 °C, the spherical micelles aggregate to a novel meander-like structure within several minutes. In its final state, the meander-like super-structure is crystalline, as revealed by time-resolved wide-angle X-ray scattering. The super-structure is shown to result from crystallization-induced aggregation of spherical micelles. Moreover, crystallization leads to well-defined angles between subsequent aggregating units. A quantitative Avrami-type analysis of the crystallization kinetics demonstrates that the formation of the meander-type structure resembles a 2D growth process combined with a breakout crystallization, showing an Avrami-exponent of 2.5. In contrast to this, crystallization at low temperatures resembles a confined crystallization with a low Avrami-exponent of 0.7. All data demonstrate that the morphology of block copolymers having a crystallizable block can be switched by the competition of aggregation and crystallization.

PDMAEMA-Grafted Core–Shell–Corona Particles for Nonviral Gene Delivery and Magnetic Cell Separation

Monodisperse, magnetic nanoparticles as vectors for gene delivery were successfully synthesized via the grafting-from approach. First, oleic acid stabilized maghemite nanoparticles (γ-Fe2O3) were encapsulated with silica utilizing a reverse microemulsion process with simultaneous functionalization with initiating sites for atom transfer radical polymerization (ATRP). Polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA) from the core-shell nanoparticles led to core-shell-corona hybrid nanoparticles (γ-Fe2O3@silica@PDMAEMA) with an average grafting density of 91 polymer chains of DP(n) = 540 (PDMAEMA540) per particle. The permanent attachment of the arms was verified by field-flow fractionation. The dual-responsive behavior (pH and temperature) was confirmed by dynamic light scattering (DLS) and turbidity measurements. The interaction of the hybrid nanoparticles with plasmid DNA at various N/P ratios (polymer nitrogen/DNA phosphorus) was investigated by DLS and zeta-potential measurements, indicating that for N/P ≥ 7.5 the complexes bear a positive net charge and do not undergo secondary aggregation. The hybrids were tested as transfection agents under standard conditions in CHO-K1 and L929 cells, revealing transfection efficiencies >50% and low cytotoxicity at N/P ratios of 10 and 15, respectively. Due to the magnetic properties of the hybrid gene vector, it is possible to collect most of the cells that have incorporated a sufficient amount of magnetic material by using a magnetic activated cell sorting system (MACS). Afterward, cells were further cultivated and displayed a transfection efficiency of ca. 60% together with a high viability.