Layer-by-layer assembly of microcapsules and their biomedical applications

Nanoengineered multifunctional capsules with tailored structures and properties are of particular interest due to their multifunctions and potential applications as new colloidal structures in diverse fields. Among the available fabrication methods, the layer-by-layer (LbL) assembly of multilayer films onto colloidal particles followed by selective template removal has attracted extensive attention due to its advantages of precise control over the size, shape, composition, wall thickness and functions of the obtained capsules. The past decade has witnessed a rapid increase of research concerning the new fabrication strategies, functionalization and applications of this kind of capsules, particularly in the biomedical fields such as drug delivery, biosensors and bioreactors. In this critical review, the very recent progress of the multilayer capsules is summarized. First, the advances in assembly of capsules by the LbL technique are introduced with focus on tailoring the properties of hydrogen-bonded multilayer capsules by cross-linking, and fabrication of capsules based on covalent bonding and bio-specific interactions. Then the fabrication strategies which can speed up capsule fabrication are reviewed. In the following sections, the multi-compartmental capsules and the capsules that can transform their shape under stimulus are presented. Finally, the biomedical applications of multilayer capsules with particular emphasis on drug carriers, biosensors and bioreactors are described (306 references).     

Layer-by-layer assembly of multilayer films of polyoxometalates and tris(phenanthrolinedione) complexes of transition metals

A series of organic-inorganic composite films were prepared by the layer-by-layer self-assembly method containing the phendione complexes of transition metals [M(phendione)₃]²⁺ (M=Fe²⁺, Co²⁺, phendione=1,10-phenanthroline-5,6-dione) and the polyoxometalates (POMs). UV-vis spectroscopy was used to follow the fabrication process of (BW₁₂/[M(phendione)₃]²⁺)_n (BW₁₂=BW₁₂O₄₀⁵⁻, M=Fe²⁺, Co²⁺) and (Co₄(PW₉)₂/[M(phendione)₃]²⁺)_n (Co₄(PW₉)₂=Co₄(H₂O)₂(PW₉O₃₄)₂¹⁰⁻, M=Fe²⁺, Co²⁺) multilayer films. Electrochemical studies on the films illustrate that the POM species exhibit well-defined redox peaks and the phendione species show pH-dependent electrochemical behavior. The photoluminescent properties were investigated to show the (BW₁₂/[Fe(phendione)₃]²⁺)_n film with low-energey red photoluminescence at 672 nm.     

Layer-by-layer assembly on stimuli-responsive microgels

From flat and rigid substrates to hard and rigid particles, the complexity of shape and size of templates have taken new dimensions with the advent of new class of soft nanomaterials obtained from more conventional polymeric structures. This review focuses mainly on the layer-by-layer assembly on soft and porous stimuli-responsive microgels with particular emphasis on recent advances and developments made in recent years.     

Layer-by-layer assembly of metal-mediated multiporphyrin arrays

Two types of multiporphyrin arrays, mediated by PdCl4(2-) complex ions at the air-water interface, were alternately transferred onto solid supports to form three-dimensional organized multilayers by a layer-by-layer method.     

Layer-by-layer assembly of ordinary and composite coordination multilayers

Coordination self-assembly of bishydroxamate-based metal-organic multilayers on gold employing a layer-by-layer (LbL) approach was investigated. It is shown that the solution chemistry of the participating metal ion has a marked influence on the composition and properties of the multilayers. Use of Ce4+ and particularly zirconium(IV) acetylacetonate (Zr(acac)4) solutions in the ion-binding step of multilayer construction leads to multilayers with a near-stoichiometric metal ion-to-ligand ratio, suggesting a structure close to that predicted by a simple coordination self-assembly scheme. On the other hand use of a ZrCl4 solution as the source of metal ions in the multilayer construction leads to a multilayer with greater thickness and a large excess of Zr(IV), evenly distributed between the organic layers. In the latter case, a ratio of ca. 1:2 between the excess Zr and oxygen, as well as long-term Zr4+ binding experiments showing deposition of ZrO2, suggest the formation of a zirconia-type nanophase between the bishydroxamate organic repeat units during multilayer self-assembly. Hence, while the multilayer prepared using Zr(acac)4 solution appears to represent a "true" coordination-based structure, the one prepared using ZrCl4 is best described as a composite organic-ceramic multilayer. Composite multilayers prepared in this way display different properties from those of the stoichiometric ones, such as improved dielectric behavior and higher stiffness. Even greater mechanical stability is obtained with multilayers constructed using alternate binding of ZrCl4 and Ce4+. The concept of LbL formation of coordination-based composite organic-ceramic structures may be useful in obtaining nanometer-scale structures with tunable properties.     

Layer-by-layer assembly: from conventional to unconventional methods

Layer-by-layer (LbL) assembly is a powerful means for fabricating multilayer thin films with controlled architecture and composition. This feature article discusses different types of methods for LbL assembly. On the one hand, some of the conventional LbL methods are introduced, which are driven by electrostatic interactions, hydrogen bonds, step-by-step reactions, sol-gel processes, molecular recognition, charge-transfer, stepwise stereocomplex assembly, and electrochemistry. On the other hand, some of the unconventional methods for fabricating of the building blocks which can not be assembled by conventional methods are also summarized. These unconventional methods usually involve the formation of supramolecular structures via one type of self-assembly. These structures can subsequently be used as building blocks in another type of self-assembly. To take advantage of these conventional and unconventional methods, a great number of building blocks can be fabricated into multilayer thin films with a defined sequence structure in a designed way. It has been demonstrated that LbL methods provide new horizons for surface molecular engineering.     

Layer-by-layer assembly for rapid fabrication of thick polymeric films

In the past two decades, layer-by-layer (LbL) assembly has been proven to be a convenient and versatile method to fabricate functional films. However, using traditional dipping LbL assembly to fabricate micrometer-thick films is time consuming. Compared with ultrathin films, micrometer-thick films prepared by LbL assembly possess enhanced mechanical stability, and allow deposition of a significantly increased amount of materials and the integration of multiple functions. These merits of thick films produced by LbL assembly can result in new functions and allow the functions of ultrathin films fabricated by LbL assembly to be optimized. In this tutorial review, the methods for rapid fabrication of thick polymeric films involving LbL assembly are reviewed. The functions of such films that are relevant to their micrometer thickness are discussed.     

Hydrothermal assembly and luminescence property of lanthanide-containing Anderson polyoxometalates

Two compounds, {[Sm(H₂O)₅]₂(TeMo₆O₂₄)}·6H₂O (1) and {[Eu(H₂O)₇]₂ (TeMo₆O₂₄)}·5H₂O (2) have been synthesized by hydrothermal reactions and characterized by elemental analyses, IR spectra, thermal stability analyses, X-ray powder diffraction, and single-crystal X-ray diffraction. Compound 1 represents the first example of a 2D layer architecture constructed from Anderson-type polyoxoanions [TeMo₆O₂₄]⁶⁻ and rare-earth ions Ln³⁺. Compound 2 displays a 1D chain structure built up of alternating Anderson-type polyoxoanions [TeMo₆O₂₄]⁶⁻ and rare-earth ions Eu³⁺ along the c-axis. Luminescence measurement of 2 exhibits typical red fluorescent emission of the Eu³⁺ ion at room temperature. Furthermore, the emission is intense enough to be observed macroscopically under UV irradiation (365 nm).     

Preparation parameter development for layer-by-layer assembly of Keggin-type polyoxometalates

Polyoxometalates possess many useful properties for electrochemical catalysis. These molecule-size clusters can be assembled into thin films through the layer-by-layer method. In this study, we determined a cluster concentration range within which layer-by-layer (LbL) films have been successfully fabricated. We also find the influence of salt added to the deposition solutions. In an attempt to understand the self-assembly process at the molecular level, thermodynamic arguments, derived from complexation between nanoscale particles and oppositely charged polyelectrolyte chains, have been employed to interpret the adsorption of polyoxometalate clusters onto a cationic polymer layer. The scaling results describe the contact mode between a polymer chain and a cluster. The assembly can be visualized with assistance by understanding the contact between the polymer chain and the cluster.     

仿生微胶囊的组装及其应用

在生物物理和生物医药研究领域中,在分子水平上组装功能化的仿生微胶囊具有重要的理论和应用价值.在现有制备微胶囊的技术手段中,层层组装技术以其能够控制胶囊的尺寸、形状、囊壁的厚度和组成以及易于实现功能化等特点,引起了人们越来越多的研究兴趣.本文将着重介绍如何利用层层组装技术,以磷脂、蛋白质和其他生物大分子为组装基元构筑仿生微胶囊、以及如何将微胶囊进行生物界面化的修饰.此外,以仿生微胶囊为药物载体,探讨其在光动力治疗方面的应用也作简单介绍.     

Layer-by-layer assembly of nacre-like nanostructured composites with antimicrobial properties

In a recent report, we have presented the layer-by-layer (LBL) assembly of a biomimetic nanostructured composite from Na(+)-montmorillonite clay nanosheets and poly(diallylmethylammonium chloride) (Tang, Z.; Kotov, N.; Magonov, S.; Ozturk, B. Nat. Mater. 2003, 2, 413). The structure, deformation mechanism, and mechanical properties of the material are very similar to those of natural nacre and lamellar bones. This fact prompts further investigation of these composites as potential bone implants. LBL assembly affords preparation of multifunctional composites, and here we demonstrate that not only mechanical strength, but also antibacterial activity, can be introduced in these implantable materials by alternating clay layers with starch-stabilized silver nanoparticles. The resulting composite showed excellent structural stability with no detectable levels of silver lost over a 1 month period. Evaluation of the antibacterial properties showed almost complete growth inhibition of E. coli over an 18 h period. The amount of silver eluted from the LBL composite over a 1 month period was determined to be only 0.5-3.0 microg/L. This concentration of silver did not prevent the growth of the mammalian tissue cultures. The LBL composite has shown biocompatibility with the human osteoblast cell line.     

Layer-by-layer assembly of single-charged ions with a rigid polyampholyte

A novel method to produce multilayer films has been developed by layer-by-layer assembly of single-charged ions and a rigid polyampholyte containing unbalanced charges in each of its repeat units.     

Layer-by-layer assembly and spontaneous flocculation of oppositely charged oxide and hydroxide nanosheets into inorganic sandwich layered materials

Exfoliated oxide nanosheets such as Ti0.91O2 and Ca2Nb3O10 and layered double hydroxide (LDH) nanosheets of Mg2/3Al1/3(OH)2 were restacked into inorganic sandwich layered materials. Sequential adsorption of these oppositely charged nanosheets from their colloidal suspensions yielded multilayer ultrathin films while their simple mixing produced lamellar flocculates. Eliminating carbonate ions from the reaction system was found to be essential for successfully achieving the sandwich structures. The flocculated materials as well as the films were characterized by atomic force microscopy (AFM), UV-visible absorption spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), and chemical analysis, which all supported the formation of the ordered sandwich structures. AFM observations revealed alternate dense tiling of LDH nanosheets and oxide nanosheets onto a substrate surface. UV-visible absorption spectra exhibited progressive enhancement of optical density due to oxide nanosheets as a function of deposition cycles, providing strong evidence for regular growth of multilayer films. The combinations of Mg2/3Al1/3(OH)2/Ti0.91O2 and Mg2/3Al1/3(OH)2/Ca2Nb3O10 produced XRD Bragg peaks having multilayer spacings of 1.2 and 2.0 nm, respectively. These basal spacing values are compatible with the sum of thickness of LDH nanosheets and corresponding oxide nanosheets. TEM images of flocculated samples displayed lamellar features with two different constituent layers appearing alternately.     

pH-responsive polysaccharide microcapsules through covalent bonding assembly

Biocompatible and biodegradable microcapsules were fabricated by the covalent assembly of polysaccharides and their derivatives. The formation of Schiff's bases between polysaccharides and their derivatives enabled the microcapsules' autofluorescence properties and pH-responsivity. These polysaccharide microcapsules have great potential applications in biological tracing and drug delivery.     

Layer-by-layer assembly of UV-resistant poly(3,4-ethylenedioxythiophene) thin films

The layer-by-layer assembly technique was used to create electrically conductive films with poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT-PSS) and branched polyethylenimine (BPEI). Titanium dioxide (TiO(2)) and carbon black were used to prevent UV-degradation of these PEDOT-PSS thin film assemblies. Film growth and conductivity were studied, while varying composition and examining the effect of UV absorbing particles on the electrical conductivity. All films showed similar initial sheet resistances, but after exposure to 365 nm UV light for 9 days (correlating to approximately 4 years of sunlight), the films containing TiO(2) were up to 250 times more conductive. Additionally, the TiO(2) containing films were 27% more optically transparent than films made with PEDOT in the absence of TiO(2). The addition of colloidal titania allows the useful life of the PEDOT films to be extended without the detrimental effects of decreased transparency. Doping the PEDOT with dimethylsulfoxide produced eight bilayer films that were almost 6 times more conductive. However, the degradation rate for the doped PEDOT films without TiO(2) was 10 times greater than the doped films with TiO(2).     

Layer-by-layer assembly of silica-based flame retardant thin film on PET fabric

A novel method to improve flame retardant properties of textile fabric using multilayered thin films was evaluated. In this work, PET fabrics were coated with silica nanoparticles using layer-by-layer assembly. Five bilayers of positively and negatively charged colloidal silica (<10 nm average thickness) increased time to ignition and decreased heat release rate peak of PET fabric by 45% and 20%, respectively. In vertical burn test, this same nanocoating dramatically reduced burn time and eliminated melt dripping. This study demonstrates the ability to impart flame retardant behavior using a water-based, environmentally-friendly protective coating.     

Coordination-driven self-assembly of polyoxometalates into discrete supramolecular triangles

Pd(II)-directed self-assembly of a 3-pyridyl grafted Lindqvist hexavanadate led to the formation of a unique trimeric species, as confirmed by a variety of techniques, including pulsed-field gradient NMR spectroscopy and high-resolution ESI mass spectrometry.     

Layer-by-layer assembly and UV photoreduction of graphene-polyoxometalate composite films for electronics

Graphene oxide (GO) nanosheets and polyoxometalate clusters, H(3)PW(12)O(40) (PW), were co-assembled into multilayer films via electrostatic layer-by-layer assembly. Under UV irradiation, a photoreduction reaction took place in the films which converted GO to reduced GO (rGO) due to the photocatalytic activity of PW clusters. By this means, uniform and large-area composite films based on rGO were fabricated with precisely controlled thickness on various substrates such as quartz, silicon, and plastic supports. We further fabricated field effect transistors based on the composite films, which exhibited typical ambipolar features and good transport properties for both holes and electrons. The on/off ratios and the charge carrier mobilities of the transistors depend on the number of deposited layers and can be controlled easily. Furthermore, we used photomasks to produce conductive patterns of rGO domains on the films, which served as efficient microelectrodes for photodetector devices.     

Layer-by-layer self-assembled ultrathin multilayer films of lanthanide polyoxometalates and poly(allylamine hydrochloride) and their photoluminescent properties

Ultrathin multilayer films of two lanthanide polyoxometalates (LPOMs), K(17)[Eu(P(2)W(17)O(61))(2)] (EPW) and K(13)[Eu(SiW(11)O(39))(2)] (ESW), and poly(allylamine hydrochloride) (PAH) have been prepared by layer-by-layer self-assembly from dilute aqueous solutions. UV-vis spectroscopy and ellipsometry respectively show that the absorbance values at characteristic wavelengths and the thicknesses of the multilayer films increase linearly with the number of LPOM/PAH bilayers, suggesting that the deposition process is linear and highly reproducible from layer to layer. Average thicknesses of ca. 3.4 and 2.4 nm were determined for the EPW/PAH and ESW/PAH bilayers by ellipsometry, respectively. In addition, scanning electron microscopy (SEM) and atomic force microscopy (AFM) images provide the surface morphology of the LPOM/PAH films, indicating that the film surface is relatively uniform and smooth. The photoluminescent properties of these films have also been investigated by fluorescence spectroscopy. The LPOM/PAH multilayer film has a good thermal stability as shown by UV-vis, X-ray photoelectron, and fluorescence spectra.     

Layer-by-layer assembly of zeolite crystals on glass with polyelectrolytes as ionic linkers

ZSM-5 crystals and glass plates tethered with trimethylpropylammonium iodide and sodium butyrate, respectively, (denoted as Z+, Z-, G+, and G-, respectively) were prepared. Treatment of G- with Z+ suspended in ethanol results in monolayer assembly of Z+ on G- (G-/Z+) with high surface coverage. The zeolite crystals have a strong tendency to closely pack and align with the b-axis normal to the glass plate, despite large positive zeta potentials. Subsequent treatment of G-/Z+ with Z- leads to second-layer assembly of Z- on G-/Z+ (G-/Z+/Z-), but with rather poor coverage. Sequential treatment of G+ with poly(sodium 4-styrenesulfonate)(Na+PSS-), poly(diallyldimethylammonium chloride) (PDDA+Cl-), and Na+PSS- followed by Z+ yields glass plates assembled with monolayers of Z+ with very high surface coverage through the composite polyelectrolyte linkers (G+/PSS-/PDDA+/PSS-/Z+). The zeolite crystals also have a strong tendency to closely pack and align with the b-axis perpendicular to the substrate plane. The binding strength between the zeolite crystals and glass plates is much higher in G+/PSS-/PDDA+/PSS-/Z+ than in G-/Z+. Repetition of the sequential PSS-/PDDA+/PSS-/Z+ layering for five cycles yields glass plates assembled with pentalayers of ZSM-5 crystals [G+/(PSS-/PDDA+/PSS-/Z+)(5)]. The observed degrees of coverage and alignment of zeolite crystals in each layer were very high up to the third layers despite the nonuniformity of the sizes and shapes of the zeolite crystals used in this study. This report thus demonstrates the feasibility of layer-by-layer assembly of micrometer-sized zeolite crystals on glass through electrostatic interaction between surface-bound, full-fledged ionic centers, especially by use of polyelectrolyes as the linkers.