Shin-ichi Yusa

Preparation and characterization of a pH-responsive nanogel based on a photo-cross-linked micelle formed from block copolymers with controlled structure.

Poly(ethylene glycol)-b-poly(2-(diethylamino)ethyl methacrylate-co-2-cinnamoyloxyethyl acrylate) (PEG-b-P(DEAEMA/CEA)) was prepared by reversible addition-fragmentation chain transfer (RAFT)-controlled radical polymerization. As solution pH is increased from an acidic pH, the hydrodynamic radius (R(h)) increases abruptly near pH 7, indicative of the micelle formation at pH > 7. The micelle formation at pH > 7 was supported by (1)H NMR and light scattering data. Upon irradiation of light, polymer chains in the core of the polymer micelle are cross-linked as a result of the photodimerization of the cinnamoyl groups, yielding a nanogel. The nanogel was characterized by gel-permeation chromatography (GPC), light scattering, small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM), and fluorescence techniques. The nanogel displayed an ability to solubilize N-phenyl-1-naphthylamine (PNA) and 1-pyrenemethanol (hydrophobic guest molecules) into the hydrophobic core at pH > 7. It was confirmed with PNA that the solubilization of a guest molecule occurred at polymer concentrations (C(p)) lower than the critical micelle concentration (cmc) for PEG-b-P(DEAEMA/CEA) because the nanogel retains its micellar structure at C(p) < cmc. 1-Pyrenemethanol is strongly captured by the nanogel at pH 10, whereas it is easily released from the nanogel when pH is reduced to 3. This indicates that the hydrophobicity of the core of the nanogel can be modulated by a change in the degree of protonation of the DEAEMA units in the core, and thus the capture of a guest molecule and its release can be controlled by a change in solution pH.

Multifunctional Core‐Shell‐Corona‐Type Polymeric Micelles for Anticancer Drug‐Delivery and Imaging

We have developed core-shell-corona-type polymeric micelles that can integrate multiple functions in one system, including the capability of accommodating hydrophobic dyes into core and hydrophilic drug into the shell, as well as pH-triggered drug-release. The neutral and hydrophilic corona sterically stabilizes the multifunctional polymeric micelles in aqueous solution. The mineralization of calcium phosphate (CaP) on the PAA domain not only enhances the diagnostic efficacy of organic dyes, but also works as a diffusion barrier for the controlled release.

Synthesis of hollow CaCO3 nanospheres templated by micelles of poly(styrene-b-acrylic acid-b-ethylene glycol) in aqueous solutions.

An asymmetric triblock copolymer, poly(styrene-b-acrylic acid-b-ethylene glycol) (PS-b-PAA-b-PEG), was synthesized via reversible addition-fragmentation chain transfer controlled radical polymerization. Micelles of PS-b-PAA-b-PEG with PS core, PAA shell, and PEG corona were then prepared in aqueous solutions, followed by extensive characterization based on dynamic light scattering, zeta-potential, and transmission electron microscopy (TEM) measurements. The well-characterized micelles were used to fabricate hollow nanospheres of CaCO(3) as a template. It was elucidated from TEM measurements that the hollow nanospheres have a uniform size with cavity diameters of ca. 20 nm. The X-ray diffraction analysis revealed a high purity and crystallinity of the hollow nanospheres. The hollow CaCO(3) nanospheres thus obtained have been used for the controlled release of an anti-inflammatory drug, naproxen. The significance of this study is that we have overcome a previous difficulty in the synthesis of hollow CaCO(3) nanospheres. After mixing of Ca(2+) and CO(3)(2-) ions, the growth of CaCO(3) is generally quite rapid to induce large crystal, which prevented us from obtaining hollow CaCO(3) nanospheres with controlled structure. However, we could solve this issue by using micelles of PS-b-PAA-b-PEG as a template. The PS core acts as a template that can be removed to form a cavity of hollow CaCO(3) nanospheres, the PAA shell is beneficial for arresting Ca(2+) ions to produce CaCO(3), and the PEG corona stabilizes the CaCO(3)/micelle nanocomposite to prevent secondary aggregate formation.

Inorganic-organic hybrid nanoparticles with biocompatible calcium phosphate thin shells for fluorescence enhancement.

Polymeric micelles consisting of asymmetric triblock copolymers were successfully used for fabrication of robust hybrid nanoparticles with highly biocompatible calcium phosphate shells. The hydrophobic polystyrene core encapsulates hydrophobic fluorescent dyes such as Nile red. The anionic polyacrylic acid provides the site for the mineralization reaction of calcium phosphate. The polyethylene glycol corona stabilizes the hybrid nanoparticles. Fluorescent dyes can be used as imaging agents for determining the location of the nanoparticles and to give an observable indication of drug delivery, while the calcium phosphate shell can enhance the fluorescence of the encapsulated dye.

Micrometer-sized gold-silica Janus particles as particulate emulsifiers.

Micrometer-sized gold-silica Janus particles act as an effective stabilizer of emulsions by adsorption at the oil-water interface. The Janus particles were adsorbed at the oil-water interface as a monolayer and stabilized near-spherical and nonspherical oil droplets that remained stable without coalescence for longer than one year. Gold and silica surfaces have hydrophobic and hydrophilic features; these surfaces were exposed to oil and water phases, respectively. In contrast, bare silica particles cannot stabilize stable emulsion, and completed demulsification occurred within 2 h. Greater stability of the emulsion for the Janus particle system compared to the silica particle system was achieved by using the adsorption energy of the Janus particles at the oil-water interface; the adsorption energy of the Janus particles is more than 3 orders of magnitude greater than that of silica particles. Suspension polymerization of Janus particle-stabilized vinyl monomer droplets in the absence of any molecular-level emulsifier in aqueous media led to nonspherical microspheres with Janus particles on their surface. Furthermore, polymer microspheres carrying Au femtoliter cups on their surfaces were successfully fabricated by removal of the silica component from the Janus-particle stabilized microspheres.

Novel synthesis route for Ag@SiO2 core–shell nanoparticles via micelle template of double hydrophilic block copolymer

We report a new strategy for synthesizing core–shell nanoparticles of Ag@SiO2 templated by a complex micelle of silver ions and a double hydrophilic block copolymer, poly[3-(methacryloylamino) propyl trimethylammonium chloride]-block-[2-(dimethylamino) ethyl methacrylate] (PMAPTAC-b-PDMAEMA). The obtained Ag@SiO2 core–shell nanoparticles have been successfully applied as a catalyst for the reduction of p-nitrophenol.

Preparation and characterization of polyion complex micelles with phosphobetaine shells.

A pair of oppositely charged diblock copolymers, poly(2-(methacryloyloxy)ethyl phosphorylcholine)-block-poly((3-(methacryloylamino)propyl)trimethylammonium chloride) (PMPC-b-PMAPTAC) and poly(2-(methacryloyloxy)ethyl phosphorylcholine)-block-poly(sodium 2-(acrylamido)-2-methylpropanesulfonate) (PMPC-b-PAMPS), was prepared via reversible addition-fragmentation chain transfer radical polymerization using a PMPC-based macro chain transfer agent. The pendant phosphorylcholine group in the hydrophilic PMPC block has anionic phosphate and cationic quaternary amino groups, which are neutralized within the pendant group. Therefore, the mixing of aqueous solutions of PMPC-b-PMAPTAC and PMPC-b-PAMPS leads to the spontaneous formation of simple core-shell spherical polyion complex (PIC) micelles comprising of a segregated PIC core and PMPC shells. The PIC micelles were characterized using (1)H NMR spin-spin (T2) and spin-lattice relaxation times (T1), diffusion-ordered NMR spectroscopy, static light scattering, dynamic light scattering (DLS), and transmission electron microscopy techniques. The hydrodynamic size of the PIC micelle depended on the mixing ratio of PMPC-b-PMAPTAC and PMPC-b-PAMPS; the maximum size occurred at the mixing ratio yielding stoichiometric charge neutralization. The PIC micelles disintegrated to become unimers with the addition of salts.

Modeling Adsorption of Cationic Surfactants at Air/Water Interface without Using the Gibbs Equation

The Gibbs adsorption equation has been indispensable in predicting the surfactant adsorption at the interfaces, with many applications in industrial and natural processes. This study uses a new theoretical framework to model surfactant adsorption at the air/water interface without the Gibbs equation. The model was applied to two surfactants, C14TAB and C16TAB, to determine the maximum surface excesses. The obtained values demonstrated a fundamental change, which was verified by simulations, in the molecular arrangement at the interface. The new insights, in combination with recent discoveries in the field, expose the limitations of applying the Gibbs adsorption equation to cationic surfactants at the air/water interface.

Aqueous polymeric micelles of poly[N-isopropylacrylamide-b-sodium 2-(acrylamido)-2-methylpropanesulfonate] with a spiropyran dimer pendant: quadruple stimuli-responsiveness

Poly[N-isopropylacrylamide-b-sodium 2-(acrylamido)-2-methylpropane sulfonate] tagged with a spiropyran dimer at the poly(N-isopropylacrylamide) end (SP2-b-NIPAM154-b-AMPS148) was synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization to investigate multiple stimuli-responsive micelles. The micelles formed in aqueous solutions were stimulated by various chemical and physical stimuli and characterized by dynamic light scattering, scanning electron microscopy, transmission electron microscopy, UV-Vis spectroscopy and ζ-potential measurements. It was found that the block copolymer is responsive to four different types of stimulus viz. light, temperature, metal ion and pH. The NIPAM154 block gives thermo-responsiveness to the block copolymer and the AMPS148 block shows metal ion responsiveness. Due to the presence of the photochromic spiropyran moiety, the block copolymer also shows light and thermo-responsiveness. To the best of our knowledge this is the first report that deals with quadruple stimuli-responsive polymeric micelles. Such quadruple stimuli-responsive block copolymer micelles are expected to open up new applications in a variety of fields.

Synthesis of hollow BaSO4 nanospheres templated by core–shell–corona type polymeric micelles

Hollow barium sulfate (BaSO4) nanospheres were synthesized by templating a polymeric micelle of a triblock copolymer poly(styrene-b-acrylic acid-b-ethylene glycol) (PS-b-PAA-b-PEG). This polymer is known to form a micelle with a PS core, a PAA shell and a PEG corona in aqueous solutions. Barium chloride and sodium sulfate were used as precursors of BaSO4. In the synthesis, the PS core acts as a template for cavities of the hollow particles, the PAA shell is beneficial for arresting Ba2+ ions to produce BaSO4, and the PEG corona stabilizes the BaSO4/polymer nanocomposite to prevent secondary aggregate formation. Hollow BaSO4 nanospheres were obtained by removing the polymeric template from the BaSO4/polymer nanocomposite by calcination. The hollow BaSO4 nanospheres thus fabricated were characterized by various techniques including transmission electron microscopy and X-ray diffraction analysis. The average diameter of the spheres is around 25 nm and the average cavity diameter is around 16 nm. The significance of the present method is that it can avoid formation of large crystals which is generally unavoidable in other methods.