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Vaccine adjuvants that can induce robust protective immunity are highly sought after for the development of safer and more effective vaccines. Vaccine formulation parameters that govern efficacy are still far from clear, such as the diverse impacts of codelivering agonist molecules for innate cell receptors (e.g., pattern recognition receptors). In this study, a mesoporous silica-templating approach is used to fabricate protein antigen (ovalbumin) particles covalently functionalized with agonists for NOD-like receptor 2 (NOD2) and Toll-like receptor 9 (TLR9). Particle-induced combinatorial NOD2/TLR9 signaling results in synergistic inflammatory cytokine secretion by mouse macrophages (RAW 264.7). Administration of NOD2/TLR9 particles in mice results in adaptive immune responses that are both quantitatively and qualitatively different than those resulting from administration of particles conjugated with either NOD2 or TLR9 agonists alone. While delivery of NOD2 agonists alone activates T helper 2 (Th2)-type responses (and no CD8+ T cell activation) and delivery of TLR9 agonists alone activates CD8+ T cell and T helper 1 (Th1)-type responses, codelivery of NOD2 and TLR9 agonists enhances Th1-type responses and abrogates CD8+ T cell activation. The results illustrate that in the particle-based system, NOD2 activation plays different roles in polarizing adaptive immune responses depending on coactivation of TLR9.

The rational design and engineering of metal–organic framework (MOF) crystals with hollow features has been used for various applications. Here, a top-down strategy is established to construct hollow MOFs via synergistic etching and surface functionalization by using phenolic acid. The macrosized cavities are created inside various types of MOFs without destroying the parent crystalline framework, as evidenced by electron microscopy and X-ray diffraction. The modified MOFs are simultaneously coated by metal–phenolic films. This coating endows the MOFs with the additional functionality of responding to near infrared irradiation to produce heat for potential photothermal therapy applications.

The assembly of low-fouling polymer capsules with redox-responsive behavior and intracellular degradability is reported. Thiol-containing poly(2- ethyl-2-oxazoline) (PEtOxMASH) brushes are synthesized by atom transfer radical polymerization (ATRP) of oligo(2-ethyl-2-oxazoline)methacrylate and glycidyl methacrylate (GMA) and subsequent ring-opening reaction of the GMA. Sequential deposition of PEtOxMA SH /poly(methacrylic acid) (PMA) multilayers onto silica (SiO2) particle templates and crosslinking through disulfide formation yield stable capsules after the removal of the SiO2 templates by buffered hydrofl uoric acid (HF). The redox-responsive nature of the disulfide crosslinking groups enables the degradation of these capsules under simulated intracellular conditions at pH 5.9 and 5 m M glutathione (GSH). Furthermore, capsule degradation is observed after incubation with dendritic (JAWS II) cells. Even at high capsule-to-cell ratios, PEtOxMASH capsules show only negligible cytotoxicity. Quartz crystal microgravimetry (QCM) studies, using 100% human serum, reveal that films prepared from PEtOxMASH exhibit low-fouling properties. The degradation and low-fouling properties are promising for application of PEtOxMASH films/capsules for the delivery and triggered release of therapeutics.

The preparation of pH-labile polymer-drug particles via mesoporous silica-templated assembly for anticancer drug delivery into cancer cells is reported. The polymer-drug conjugate is synthesized via thiol-maleimide click chemistry using thiolated poly(methacrylic acid) (PMASH) and a pH-labile doxorubicin (Dox) derivative. Drug-loaded polymer particles that are stable under physiological conditions are obtained through infiltration of the conjugates into mesoporous silica particles, followed by cross-linking the PMASH chains, and subsequent removal of the porous silica templates. The encapsulated Dox is released from the particles through cleavage of the hydrazone bonds between Dox and PMASH at endosomal/lysosomal pH. Cell viability assays show that the assembled PMASH particles have negligible cytotoxicity to LIM1899 human colorectal cancer cells. In comparison, Dox-loaded PMASH particles cause significant cell death following internalization. The reported particles represent a novel and versatile class of stimuli-responsive carriers for controlled drug delivery.

The preparation of monodisperse polymer (polydopamine, PDA) capsules by a one-step interfacial polymerization of dopamine onto dimethyldiethoxysilane (DMDES) emulsion droplets and removal of the DMDES templates with ethanol is reported. The diameters of the PDA capsules can be tailored from 400 nm to 2.4 μm by varying either the DMDES emulsion condensation time or the emulsion concentration used for templating. Further, capsules with defined nanometer-scale shell thicknesses (ranging from ∼10 to 30 nm) can be prepared by adjusting the emulsion concentration. This shell thickness can be increased by repeated interfacial polymerization of dopamine, with three cycles yielding capsules with a shell thickness of up to 140 nm (for a 0.6% v/v suspension). Functional substances, such as organically stabilized magnetic (Fe3O4) nanoparticles, quantum dots (CdSe/CdS), and hydrophobic drugs (thiocoraline), can be preloaded in the emulsion droplets, and following PDA coating and DMDES removal, these materials remain encapsulated in the polymer capsules. All of the unloaded and loaded PDA capsules are monodisperse and do not aggregate. This work provides new avenues for the preparation of polymer capsules with defined size and shell thickness and for the encapsulation of a range of hydrophobic substances. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Therapeutic artificial cells or organelles are nanoengineered vehicles that are expected to substitute for missing or lost cellular function. The creation of capsosomes, polymer carrier capsules containing liposomal subcompartments, is a promising approach towards constructing such therapeutic devices using the layer-by-layer assembly method. Herein, the assembly of intact, nonaggregated capsosomes containing multiple liposome layers is reported. It is also further demonstrated that thiocoraline, a hydrophobic model peptide with antitumor activity, can be efficiently loaded into the membrane of the liposomal subcompartments of the capsosomes. Cell viability assays verify the activity of the trapped antitumor cargo. It is also shown that pristine capsosomes do not display inherent cytotoxic effects. The ability to tune the number of liposome layers and hence the drug loading in capsosomes as well as their noncytotoxicity provide new opportunities for the creation of therapeutic artificial cells and organelles.

A versatile sensing method based on monodisperse liquid crystal (LC) emulsion droplets detects and distinguishes between different types of bacteria (Gram +ve and −ve) and viruses (enveloped and non-enveloped). LCs of 4-cyano-4'-pentylbiphenyl transition from a bipolar to radial configuration when in contact with Gram −ve bacteria (E. coli) and lipid-enveloped viruses (A/NWS/Tokyo/67). This transition is consistent with the transfer of lipid from the organisms to the interfaces of the micrometer-sized LC droplets. In contrast, a transition to the radial configuration is not observed in the presence of Gram +ve bacteria (Bacillus subtilis and Micrococcus luteus) and non-enveloped viruses (M13 helper phage). The LC droplets can detect small numbers of E. coli bacteria (1–5) and low concentrations (104 pfu mL−1) of A/NWS/Tokyo/67 virus. Monodisperse LC emulsions incubated with phosholipid liposomes (similar to the E. coli cell wall lipid) reveal that the orientational change is triggered at an area per lipid molecule of ∼46 A2 on an LC droplet (∼1.6 × 108 lipid molecules per droplet). This approach represents a novel means to sense and differentiate between types of bacteria and viruses based on their cell-wall/envelope structure, paving the way for the development of a new class of LC microdroplet-based biological sensors.

The ability to reliably engineer surfaces with nanoscale precision is a rapidly developing field of research with applications ranging from biosensing and biomedical materials to antifouling and corrosion protection. The layer-by-layer (LbL) approach is a widely utilized method for engineering surfaces, in part because of the large array of polymeric materials that can be integrated and the diverse range of functionality that these materials afford. Herein, we discuss the LbL deposition of multicomponent 'blend' solutions to form polyelectrolyte blend multilayer films and coatings. This approach is a versatile platform for enhancing film stability, incorporating a wide range of functional materials, controlling film morphology and material properties, and increasing biological response, thereby expanding the range of potential applications. © 2008 WILEY-VCH Verlag GmbH & Co. KGaA.

Hydrogen-bonding interactions are an important alternative to electrostatic interactions for assembling multilayer thin films of uncharged components. Herein, a new method is reported for rendering such films stable at pH values close to physiological conditions. Multilayer films based on hydrogen bonding are assembled by the alternate deposition of poly[(styrene sulfonic acid)-co-(maleic acid)] (PSSMA) and poly(N-isopropylacrylamide) (PNiPAAm) at pH 2.5. The use of PSSMA results in multilayers that contain free styrene sulfonate groups, as these moieties do not interact with the PNiPAAm functional groups. Subsequent infiltration of a multivalent ion (Ce 4+ or Fe 3+ ) leads to an increase in the total film mass, with little impact on the film morphology, as determined by using atomic force microscopy. To examine the film stability, the resulting films have been exposed to elevated pH (7.1). While there is substantial swelling of the multilayers (25 % and 55 % for Ce 4+ - and Fe 3+ -stabilized films, respectively), film loss is negligible. This provides a stark contrast with non-stabilized films, which disassemble almost immediately upon exposure to pH7.1. This method represents a simple and effective strategy for stabilizing hydrogen-bonded structures non-covalently. Further, the multivalent ions also render the films responsive to changes in the local redox environment, as demonstrated by film disassembly after exposure of Fe 3+ -treated films to iodide solutions.

A simple and effective method is described for the fabrication of robust zeolitic membranes with three-dimensional (3D) interconnected macroporous structures. The membranes were prepared by electrostatically seeding mesoporous silica sphere (MSS) self-assembled films with silicalite-1 nanoparticles, followed by hydrothermal treatment. The membrane thickness, which is determined by the MSS film thickness, can be easily adjusted from tens to hundreds of micrometers by varying the concentration of the MSS dispersion and the solution volume. Biomacromolecule-functionalized macroporous zeolitic membrane bioreactors were subsequently prepared via the layer-by-layer (LbL) electrostatic assembly of polyelectrolytes and enzyme (catalase) on the 3D macroporous membranes. The enzyme-modified membranes with interconnected macroporous structures display enzyme loading amounts and activities that are one order of magnitude higher than corresponding 3D zeolite films with closed macropores, and approximately three orders of magnitude higher than their non-porous planar film counterparts assembled on silica substrates. The enzyme loadings and activities were found to be approximately linearly dependent on the thicknesses of the membranes. Furthermore, the immobilized enzyme exhibits enhanced reaction stability in comparison with enzyme in bulk solution. These membranes are potentially useful for separations as they could be used to simultaneously perform reaction and separation steps.

The formation of weak polyelectrolyte films on planar and spherical supports has recently evoked major interest, as such coatings allow novel material properties to be tunable by pH and salt adjustment of the polyelectrolyte deposition conditions. We report on the build up of multilayers of the weak polyelectrolytes poly(acrylic acid) (PAA) and poly(allylamine hydrochloride) (PAH) on submicrometer-sized polystyrene (PS) and silica colloid spheres (∼ 500 nm) with the aid of copper ion templating. The copper ions complex to the carboxylate groups of PAA, facilitating the formation of PAA/PAH multilayers on the particles. Regular growth of the layers on the colloid spheres with each polyelectrolyte deposition step was confirmed by microelectrophoresis, single-particle light scattering (SPLS), and transmission electron microscopy (TEM), with an average bilayer thickness of ∼ 3 nm. The polyelectrolyte multilayer-coated particles formed stable colloidal dispersions, with ζ-potentials ranging from 30 mV (PAH outer layer) and –50 mV (PAA outer layer). Complementary quartz-crystal microbalance and UV-vis spectrophotometry studies on PAA/PAH multilayers formed on planar supports were performed to examine the film formation and the role of copper ion binding to the layers. PAA/PAH multilayers formed on colloid particles were also chemically crosslinked by using the activator 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). The degree of film crosslinking could be readily controlled by varying the concentration of EDC employed. Following solvent decomposition of the template particles coated with crosslinked PAA/PAH multilayers, intact hollow polymer capsules were obtained. These capsules were found to be impenetrable to polystyrene.