Hirotaka Ejima

One-Step Assembly of Coordination Complexes for Versatile Film and Particle Engineering

One-Step Coverage Controllable formation of thin films often requires slow deposition conditions or multiple rounds of coating. Ejima et al. (p. 154; see the Perspective by Bentley and Payne) report a simple and versatile method for coating surfaces with thin biocompatible films made from the condensation of Fe3+ ions and a natural polyphenol, tannic acid, from aqueous solutions. Flat surfaces, colloidal particles, and even bacterial cells could be coated, and the coats could subsequently be degraded by changing the pH. Thin adherent films formed from ferric ions and a natural polyphenol, tannic acid, can coat a wide variety of surfaces. [Also see Perspective by Bentley and Payne] The development of facile and versatile strategies for thin-film and particle engineering is of immense scientific interest. However, few methods can conformally coat substrates of different composition, size, shape, and structure. We report the one-step coating of various interfaces using coordination complexes of natural polyphenols and Fe(III) ions. Film formation is initiated by the adsorption of the polyphenol and directed by pH-dependent, multivalent coordination bonding. Aqueous deposition is performed on a range of planar as well as inorganic, organic, and biological particle templates, demonstrating an extremely rapid technique for producing structurally diverse, thin films and capsules that can disassemble. The ease, low cost, and scalability of the assembly process, combined with pH responsiveness and negligible cytotoxicity, makes these films potential candidates for biomedical and environmental applications.

Engineering Multifunctional Capsules through the Assembly of Metal–Phenolic Networks

Metal-organic coordination materials are of widespread interest because of the coupled benefits of inorganic and organic building blocks. These materials can be assembled into hollow capsules with a range of properties, which include selective permeability, enhanced mechanical/thermal stability, and stimuli-responsiveness. Previous studies have primarily focused on the assembly aspects of metal-coordination capsules; however, the engineering of metal-specific functionality for capsule design has not been explored. A library of functional metal-phenolic network (MPN) capsules prepared from a phenolic ligand (tannic acid) and a range of metals is reported. The properties of the MPN capsules are determined by the coordinated metals, allowing for control over film thickness, disassembly characteristics, and fluorescence behavior. Furthermore, the functional properties of the MPN capsules were tailored for drug delivery, positron emission tomography (PET), magnetic resonance imaging (MRI), and catalysis. The ability to incorporate multiple metals into MPN capsules demonstrates that a diverse range of functional materials can be generated.

pH-Responsive Capsules Engineered from Metal–Phenolic Networks for Anticancer Drug Delivery

A new class of pH-responsive capsules based on metal-phenolic networks (MPNs) for anticancer drug loading, delivery and release is reported. The fabrication of drug-loaded MPN capsules, which is based on the formation of coordination complexes between natural polyphenols and metal ions over a drug-coated template, represents a rapid strategy to engineer robust and versatile drug delivery carriers.

Preparation of Nano- and Microcapsules by Electrophoretic Polymer Assembly†

Nanoand microcapsules are of significant interest for application in biomedicine, especially in diagnostics and therapeutic delivery. The fabrication of polymer capsules is often accomplished by the particle-mediated assembly of polymer films, whereby films are formed on particles through polymerization or by depositing multiple polymer layers through layer-by-layer (LbL) assembly. In particular, LbL assembly enables the use of particles of various types, shapes, and sizes as templates and enables a suite of polymers with different properties (functionality, responsiveness, and degradability) to be used to engineer the physical, chemical, and biological properties of the capsules. The versatility of LbL assembly with particle templates has led to the development of a range of coated particles and capsules for diverse applications, including drug and vaccine delivery. 4a–f] Despite the significant progress in the field of LbLengineered particles, the film-deposition process typically requires numerous centrifugation and rinse steps to separate the coating material (e.g., polymer) and the particles. Furthermore, it is generally limited to particles either dense and/or large enough for centrifugal sedimentation. Other methods to generate LbL capsules have also been reported: for example, atomization techniques, filter membranes, and microfluidic systems have been used; however, each of these approaches reduces the diversity of the types of particles and polymers that can be employed. These limitations highlight the necessity for the development of alternative rapid and robust approaches for the formation of LbLassembled coatings on particles to generate engineered core– shell particles and capsules. Herein, we report an electrophoretic polymer assembly (EPA) technique for depositing a range of polymers on particles of different sizes. In this approach, electrophoresis is used to generate particles coated with multiple polymer layers and, following core removal, polymer multilayer capsules. An inherent requirement of EPA is the immobilization of particles in a porous hydrogel; in this study, namely, the biologically derived polysaccharide agarose. Agarose has historically been used with electrophoresis to separate biopolymers (e.g., proteins and nucleic acids) because it gelates under ambient conditions, shows low reactivity, is easy to prepare, and has various, tunable pore sizes. In the present system, agarose acts as a “natural immobilizing microfluidic system”. However, we did not use electrophoresis to simply separate free polymer from deposited polymer, but also to deposit the polymers on immobilized particles (Figure 1). This technique reduces handling times, minimizes

Endocytic pH-Triggered Degradation of Nanoengineered Multilayer Capsules

The synthesis of cross-linker free layer-by-layer (LbL) capsules that solely utilize cellular pH variations as a trigger to specifically deconstruct and subsequently release cargo in cells is reported. These capsules demonstrate retention of water-soluble therapeutic molecules as small as 500 Da at extracellular pH. Triggered capsule degradation and release of cargo is observed within 30 min of cell uptake.

Immersive Polymer Assembly on Immobilized Particles for Automated Capsule Preparation

We report a versatile approach for polymer capsule preparation using immobilized particles, which are immersed into polymer solutions either manually or by using an automated robotic dipping machine. This technique produces polyelectrolyte capsules with improved retention over conventionally prepared capsules. Additionally, responsive hydrogel capsules of different diameter can be prepared simultaneously.

Engineering Cellular Degradation of Multilayered Capsules through Controlled Cross-Linking

We report a versatile approach for controlling the intracellular degradation of polymer capsules by tailoring the degree of cross-linking in the capsules. Poly(2-diisopropylaminoethyl methacrylate) capsules were assembled by the layer-by-layer technique and covalently stabilized with a redox-responsive bisazide cross-linker using click chemistry. The degree of cross-linking, determined using radiation scintillation counting, was tuned from 65% to 98% by adjusting the amount of cross-linker used to stabilize the polymer films. Transmission electron microscopy and fluorescence microscopy studies showed that the pH responsiveness of the capsules was maintained, regardless of the degree of cross-linking. Atomic force microscopy measurements on planar surfaces revealed that increasing the degree of cross-linking decreased the film roughness (from 8.7 to 1.7 nm), hence forming smoother films; however the film thicknesses were not significantly altered. Cellular studies showed that the rate of intracellular degradation of the capsules could be controlled between 0 and 6 h by altering the degree of cross-linking in the polymer capsules. These studies also demonstrated that the cellular degradation of highly cross-linked capsules (>90%) was significantly retarded compared to degradation in simulated cellular conditions. This suggests that the naturally occurring cellular reducing environment is rapidly depleted, and there is a significant delay before the cells can replenish the reducing environment. The modular and versatile nature of this approach lends itself to application to a wide range of polymer carriers and thus offers significant potential for the design of polymer-based systems for drug and gene delivery.

Metal–Phenolic Supramolecular Gelation

Materials assembled by coordination interactions between naturally abundant polyphenols and metals are of interest for a wide range of applications, including crystallization, catalysis, and drug delivery. Such an interest has led to the development of thin films with tunable, dynamic properties, however, creating bulk materials remains a challenge. Reported here is a class of metallogels formed by direct gelation between inexpensive, naturally abundant tannic acid and group(IV) metal ions. The metallogels exhibit diverse properties, including self-healing and transparency, and can be doped with various materials by in situ co-gelation. The robustness and flexibility, combined with the ease, low cost, and scalability of the coordination-driven assembly process make these metallogels potential candidates for chemical, biomedical, and environmental applications.

Near-Incompressible Faceted Polymer Microcapsules from Metal-Organic Framework Templates

Faceted polymer microcapsules are prepared from metal-organic framework (MOF) templates. The MOF templates are removable under mild aqueous conditions. The obtained microcapsules are stiffer than their spherical counterparts, reflecting the near-incompressibility of the facet edges, and indicating that the faceting might be a useful strategy for controlling the mechanical properties of polymer microcapsules.

Biological identification of peptides that specifically bind to poly(phenylene vinylene) surfaces: Recognition of the branched or linear structure of the conjugated polymer

Peptides that bind to poly(phenylene vinylene) (PPV) were identified by the phage display method. Aromatic amino acids were enriched in these peptide sequences, suggesting that a π-π interaction is the key interaction between the peptides and PPV. The surface plasmon resonance (SPR) experiments using chemically synthesized peptides demonstrated that the Hyp01 peptide, with the sequence His-Thr-Asp-Trp-Arg-Leu-Gly-Thr-Trp-His-His-Ser, showed an affinity constant (7.7 × 10(5) M(-1)) for the target, hyperbranched PPV (hypPPV) film. This value is 15-fold greater than its affinity for linear PPV (linPPV). In contrast, the peptide screened for linPPV (Lin01) showed the reverse specificity for linPPV. These results suggested that the Hyp01 and Lin01 peptides selectively recognized the linear or branched structure of PPVs. The Ala-scanning experiment, circular dichroism (CD) spectrometry, and molecular modeling of the Hyp01 peptide indicated that adequate location of two Trp residues by forming the polyproline type II (P(II)) helical conformation allowed the peptide to specifically interact with hypPPV.