Beulah E. McKenzie

Temperature-Responsive Nanospheres with Bicontinuous Internal Structures from a Semicrystalline Amphiphilic Block Copolymer

Internally structured self-assembled nanospheres, cubosomes, are formed from a semicrystalline block copolymer, poly(ethylene oxide)-block-poly(octadecyl methacrylate) (PEO(39)-b-PODMA(17)), in aqueous dispersion. The PODMA block provides them with a temperature-responsive structure and morphology. Using cryo-electron tomography, we show that at room temperature these internally bicontinuous aggregates undergo an unprecedented order-disorder transition of the microphase-separated domains that is accompanied by a change in the overall aggregate morphology. This allows switching between spheres with ordered bicontinuous internal structures at temperatures below the transition temperature and more planar oblate spheroids with a disordered microphase-separated state above the transition temperature. The bicontinuous structures offer a number of possibilities for application as templates, e.g., for biomimetic mineralization or polymerization. Furthermore, the unique nature of the thermal transition observed for this system offers up considerable possibilities for their application as temperature-controlled release vessels.

Loading of Silica Nanoparticles in Block Copolymer Vesicles during Polymerization-Induced Self-Assembly: Encapsulation Efficiency and Thermally Triggered Release

Poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) diblock copolymer vesicles can be prepared in the form of concentrated aqueous dispersions via polymerization-induced self-assembly (PISA). In the present study, these syntheses are conducted in the presence of varying amounts of silica nanoparticles of approximately 18 nm diameter. This approach leads to encapsulation of up to hundreds of silica nanoparticles per vesicle. Silica has high electron contrast compared to the copolymer which facilitates TEM analysis, and its thermal stability enables quantification of the loading efficiency via thermogravimetric analysis. Encapsulation efficiencies can be calculated using disk centrifuge photosedimentometry, since the vesicle density increases at higher silica loadings while the mean vesicle diameter remains essentially unchanged. Small angle X-ray scattering (SAXS) is used to confirm silica encapsulation, since a structure factor is observed at q ≈ 0.25 nm–1. A new two-population model provides satisfactory data fits to the SAXS patterns and allows the mean silica volume fraction within the vesicles to be determined. Finally, the thermoresponsive nature of the diblock copolymer vesicles enables thermally triggered release of the encapsulated silica nanoparticles simply by cooling to 0–10 °C, which induces a morphological transition. These silica-loaded vesicles constitute a useful model system for understanding the encapsulation of globular proteins, enzymes, or antibodies for potential biomedical applications. They may also serve as an active payload for self-healing hydrogels or repair of biological tissue. Finally, we also encapsulate a model globular protein, bovine serum albumin, and calculate its loading efficiency using fluorescence spectroscopy.

Controlling Internal Pore Sizes in Bicontinuous Polymeric Nanospheres

Complex polymeric nanospheres were formed in water from comb-like amphiphilic block copolymers. Their internal morphology was determined by three-dimensional cryo-electron tomographic analysis. Varying the polymer molecular weight (MW) and the hydrophilic block weight content allowed for fine control over the internal structure. Construction of a partial phase diagram allowed us to determine the criteria for the formation of bicontinuous polymer nanosphere (BPN), namely for copolymers with MW of up to 17 kDa and hydrophilic weight fractions of ≤0.25; and varying the organic solvent to water ratio used in their preparation allowed for control over nanosphere diameters from 70 to 460 nm. Significantly, altering the block copolymer hydrophilic–hydrophobic balance enabled control of the internal pore diameter of the BPNs from 10 to 19 nm.

Preparation and Cross-Linking of All-Acrylamide Diblock Copolymer Nano-Objects via Polymerization-Induced Self-Assembly in Aqueous Solution

Various carboxylic acid-functionalized poly(N,N-dimethylacrylamide) (PDMAC) macromolecular chain transfer agents (macro-CTAs) were chain-extended with diacetone acrylamide (DAAM) by reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization at 70 °C and 20% w/w solids to produce a series of PDMAC–PDAAM diblock copolymer nano-objects via polymerization-induced self-assembly (PISA). TEM studies indicate that a PDMAC macro-CTA with a mean degree of polymerization (DP) of 68 or higher results in the formation of well-defined spherical nanoparticles with mean diameters ranging from 40 to 150 nm. In contrast, either highly anisotropic worms or polydisperse vesicles are formed when relatively short macro-CTAs (DP = 40–58) are used. A phase diagram was constructed to enable accurate targeting of pure copolymer morphologies. Dynamic light scattering (DLS) and aqueous electrophoresis studies indicated that in most cases these PDMAC–PDAAM nano-objects are surprisingly resistant to changes in either solution pH or temperature. However, PDMAC40–PDAAM99 worms do undergo partial dissociation to form a mixture of relatively short worms and spheres on adjusting the solution pH from pH 2–3 to around pH 9 at 20 °C. Moreover, a change in copolymer morphology from worms to a mixture of short worms and vesicles was observed by DLS and TEM on heating this worm dispersion to 50 °C. Postpolymerization cross-linking of concentrated aqueous dispersions of PDMAC–PDAAM spheres, worms, or vesicles was performed at ambient temperature using adipic acid dihydrazide (ADH), which reacts with the hydrophobic ketone-functionalized PDAAM chains. The formation of hydrazone groups was monitored by FT-IR spectroscopy and afforded covalently stabilized nano-objects that remained intact on exposure to methanol, which is a good solvent for both blocks. Rheological studies indicated that the cross-linked worms formed a stronger gel compared to linear precursor worms.

Semi-crystalline block copolymer bicontinuous nanospheres for thermoresponsive controlled release

We demonstrate the controlled release of pyrene, as a model hydrophobic molecule, from self-assembled bicontinuous nanospheres formed from an amphiphilic block copolymer. The bicontinuous polymer nanospheres act as efficient nanocarriers and the incorporation of hydrophobic poly(alkyl methacrylate) blocks introduces a temperature responsive component to the hydrophobic core.

Self-assembled Amphiphilic Block Copolymers

H. Friedrich*, B. McKenzie**, P.H.H. Bomans*, Z. Deng*, F. Nudelman*, S.J. Holder**, G. de With*, and N.A.J.M. Sommerdijk* * Laboratory of Materials & Interface Chemistry and Soft Matter CryoTEM Research Unit, Eindhoven University of Technology, Postbus 513, 5600 MB Eindhoven, The Netherlands ** Functional Materials Group, School of Physical Science, University of Kent at Canterbury, Canterbury, Kent, CT2 7NZ, United Kingdom Amphiphilic block copolymers expose the potential to self-assemble in aqueous media providing an ever expanding library of aggregate morphologies. In contrast to top down structuring approaches, self-assembly on the nanoscale has the capacity for an economical manufacture of polymeric and hybrid materials with well defined morphologies and properties. Our work examines the effects of polymer composition and preparation conditions on the aggregate structure of amphiphiles in their aqueous environment using cryogenic transmission electron microscopy (cryo-TEM) and cryo electron tomography (cryo-ET). In the present study solutions of Poly (ethylene oxide) -b- Poly (octadecyl methacrylate) (PEO-PODMA) in tetrahydrofuran (THF) were prepared at 35 ˚C followed by slow addition of water. The milky suspension was subsequently dialyzed twice in demineralized water for a total of 12 hours. Samples were stored and vitrified at 4 ˚C using a Vitrobot®. Cryo-TEM and cryo-ET were performed on the TU/e cryoTITAN microscope. As recently shown for related diblock polymers [1] also for PEO-PODMA spherical nanoaggregates with a bicontinuous internal structure were formed (Fig. 1) [2]. As we intend to use the internal aqueous compartments as selective sites where mineralization takes place a detailed analysis of the internal structure, in particular compartment size, morphology, connectivity and accessibility are key. Cryo-ET acquisition (0° to -64°; 0 to +64° at 2 ° increments) was optimized by limiting the accumulated dose to less than 70 e