Cationic Alternating Copolymerization of Vinyl Esters and 3-Alkoxyphthalides: Side Chain-Crosslinkable Polymers for Acid-Degradable Single-Chain Nanoparticles.

Cationic copolymerization of vinyl acetate and 3-alkoxyphthalides (ROPTs) was demonstrated to proceed using GaCl as a Lewis acid catalyst. Both monomers did not undergo homopolymerization, while copolymerization smoothly occurred via the crossover reactions, resulting in alternating copolymers with molecular weights of over 10. The obtained copolymers could be degraded by acid due to the cleavage of the diacyloxymethine moieties, which were derived from the crossover reactions from vinyl acetate to ROPT, in the main chain.

In Situ and Ex Situ Studies of Ring-Like Assembly of Silica Nanoparticles in the Presence of Poly(propylene oxide)-Poly(ethylene oxide) Block Copolymers.

Block copolymer-mediated self-assembly of colloidal nanoparticles has attracted great attention for fabricating various nanoparticle arrays. We have previously shown that silica nanoparticles (SNPs) assemble into ring-like nanostructures in the presence of temperature-responsive block copolymers poly[(2-ethoxyethyl vinyl ether)--(2-methoxyethyl vinyl ether)] (PEOVE-PMOVE) in an aqueous phase. The ring-like nanostructures formed within an aggregate of PEOVE-PMOVE when the temperature was increased to 45 °C, at which the polymer is amphiphilic.

Relationship between Ionic Conductivity, Glass Transition Temperature, and Dielectric Constant in Poly(vinyl ether) Lithium Electrolytes.

We report a partial elucidation of the relationship between polymer polarity and ionic conductivity in polymer electrolyte mixtures comprising a homologous series of nine poly(vinyl ether)s (PVEs) and lithium bis(trifluoromethylsulfonyl)imide. Recent simulation studies have suggested that low dielectric polymer hosts with glass transition temperatures far below ambient conditions are expected to have ionic conductivity limited by salt solubility and dissociation. In contrast, high dielectric hosts are expected to have the potential for high ion solubility but slow segmental dynamics due to strong polymer-polymer and polymer-ion interactions.

Multifunctional Traceable Liposomes with Temperature-Triggered Drug Release and Neovasculature-Targeting Properties for Improved Cancer Chemotherapy.

Poor distribution of nanocarriers at the tumor site and insufficient drug penetration into the tissue are major challenges in the development of effective and safe cancer therapy. Here, we aim to enhance the therapeutic effect of liposomes by accumulating doxorubicin-loaded liposomes at high concentrations in and around the tumor, followed by heat-triggered drug release to facilitate low-molecular-weight drug penetration throughout the tumor. A cyclic RGD peptide (cRGD) was incorporated into liposomes decorated with a thermosensitive polymer that allowed precise tuning of drug release temperature (i.

Precise synthesis of amphiphilic diblock copolymers consisting of various ionic liquid-type segments and their influence on physical gelation behavior in water.

Appropriately designed amphiphilic diblock vinyl ether (VE) copolymers consisting of an ionic liquid-type segment and a hydrophobic segment were demonstrated to undergo physical gelation in water at extremely low concentrations. The precursor diblock copolymers were synthesized by the living cationic polymerization of 2-chloroethyl VE with a hydrophobic VE through an appropriately designed initiating system such as optimized temperature and catalyst. A relatively high temperature such as 20 °C was important for controlled polymerization of octadecyl VE.

tert-Butyl Esters as Potential Reversible Chain Transfer Agents for Concurrent Cationic Vinyl-Addition and Ring-Opening Copolymerization of Vinyl Ethers and Oxiranes.

tert-Butyl esters are demonstrated to function as chain transfer agents (CTAs) in the cationic copolymerization of vinyl ether (VE) and oxirane via concurrent vinyl-addition and ring-opening mechanisms. In the copolymerization of isopropyl VE and isobutylene oxide (IBO), the IBO-derived propagating species reacts with tert-butyl acetate to generate a copolymer chain with an acetoxy group at the ω-end. This reaction liberates a tert-butyl cation; hence, a polymer chain with a tert-butyl group at the α-end is subsequently generated.

Tandem Unzipping and Scrambling Reactions for the Synthesis of Alternating Copolymers by the Cationic Ring-Opening Copolymerization of a Cyclic Acetal and a Cyclic Ester.

Cationic copolymerization of different types of monomers, 4-hydroxybutyl vinyl ether (HBVE) and ε-caprolactone (CL), was explored using EtSOH as an acid catalyst, producing copolymers with a remarkably wide variety of compositions and sequences. In the initial stage of the reaction, HBVE was unexpectedly isomerized to 2-methyl-1,3-dioxepane (MDOP), followed by concurrent copolymerization of MDOP and CL via active chain end and activated monomer mechanisms, respectively. The compositions and sequences of the copolymers were tunable, depending on the initial monomer concentrations.

Desilylation-Triggered Degradable Silylacetal Polymers Synthesized via Controlled Cationic Copolymerization of Trimethylsilyl Vinyl Ether and Cyclic Acetals.

Silylacetal was demonstrated to function as a promising cleavable moiety for preparing polymers degradable via desilylation under diverse, mild conditions. The silylacetal moieties were installed in the main chain of the polymers via the controlled cationic copolymerization of trimethylsilyl vinyl ether (TMSVE) and a cyclic acetal under appropriately designed conditions. Importantly, desilylation reactions of the silylacetal units occurred under weak acid, base, or fluoride ion conditions, which triggered the degradation of the polymer via the spontaneous cleavage of the unstable hemiacetal moieties generated by the desilylation.

Bioinspired Approach to Silica Nanoparticle Synthesis Using Amine-Containing Block Copoly(vinyl ethers): Realizing Controlled Anisotropy.

Core-shell polymer-silica hybrid nanoparticles smaller than 50 nm in diameter were formed in the presence of micelles of poly(2-aminoethyl vinyl ether--isobutyl vinyl ether) (poly(AEVE--IBVE)) through the hydrolysis and polycondensation of alkoxysilane in aqueous solution at a mild pH and temperature. The size of the nanoparticles as well as the number and size of the core parts were effectively controlled by varying the molecular weight of the copolymers. The polymers could be removed by calcination to give hollow silica nanoparticles with Brunauer-Emmett-Teller surface areas of more than 500 m g.

Cationic Ring-Opening Co- and Terpolymerizations of Lactic Acid-Derived 1,3-Dioxolan-4-ones with Oxiranes and Vinyl Ethers: Nonhomopolymerizable Monomer for Degradable Co- and Terpolymers.

Lactic acid-derived 1,3-dioxolan-4-ones (DOLOs), which do not undergo cationic homopolymerization, were demonstrated to yield copolymers with oxiranes through a cationic copolymerization via frequent crossover reactions. Acetal and ester moieties were generated in the main chain of the copolymers via crossover reactions from DOLO to oxirane and from oxirane to DOLO, respectively, which is in contrast to the unsuccessful generation of hemiacetal ester moieties in the homopropagation of DOLO. In addition, the terpolymerization of DOLO, oxirane, and vinyl ether (VE) proceeded via crossover reactions, while copolymers could not be generated from VE and DOLO in the absence of oxirane.

Ring-Like Assembly of Silica Nanospheres in the Presence of Amphiphilic Block Copolymer: Effects of Particle Size.

Block copolymer-mediated self-assembly of colloidal nanoparticles has attracted great attention for the fabrication of a wide variety of nanoparticle arrays. We have previously shown that silica nanospheres (SNSs) 15 nm in diameter assemble into ring-like nanostructures in the presence of amphiphilic block copolymers poly[(2-ethoxyethyl vinyl ether)- block-(2-methoxyethyl vinyl ether)] (EOVE-MOVE) in an aqueous phase. Here, the effects of particle size of SNSs on this polymer-mediated self-assembly are studied systematically using scanning electron microscopy to observe SNSs of seven different sizes between 13 to 42 nm.

Heterogeneous adhesion of cells on polymer surfaces with underlying amorphous/crystalline phases.

Fibroblastic adhesion behaviour on films of a poly[(2-methoxyethyl vinyl ether) (PMOVE)-block-(l-lactic acid) (PLLA)], in which the surface was covered with PMOVE, was studied. Fibroblasts were sufficiently sensitive to identify crystalline/non-crystalline regions existing beneath the surface PMOVE layer.

Aggregation of Cationic Amphiphilic Block and Random Copoly(vinyl ether)s with Antimicrobial Activity.

In this study, we investigated the aggregation behaviors of amphiphilic poly(vinyl ether)s with antimicrobial activity. We synthesized a di-block poly(vinyl ether), B38, composed of cationic primary amine and hydrophobic isobutyl (Bu) side chains, which previously showed antimicrobial activity against . B38 showed similar uptake behaviors as those for a hydrophobic fluorescent dye, 1,6-diphenyl-1,3,5-hexatriene, to counterpart polymers including homopolymer H44 and random copolymer R40, indicating that the Bu block does not form strong hydrophobic domains.

Tandem Reaction of Cationic Copolymerization and Concertedly Induced Hetero-Diels-Alder Reaction Preparing Sequence-Regulated Polymers.

A unique tandem reaction of sequence-controlled cationic copolymerization and site-specific hetero-Diels-Alder (DA) reaction is demonstrated. In the controlled cationic copolymerization of furfural and 2-acetoxyethyl vinyl ether (AcOVE), only the furan ring adjacent to the propagating carbocation underwent the hetero-DA reaction with the aldehyde moiety of another furfural molecule. A further and equally important feature of the copolymerization is that the obtained copolymers had unprecedented 2:(1 + 1)-type alternating structures of repeating sequences of two VE and one furfural units in the main chain and one furfural unit in the side chain.

Evaluation of a combination tumor treatment using thermo-triggered liposomal drug delivery and carbon ion irradiation.

The combination of radiotherapy with chemotherapy is one of the most promising strategies for cancer treatment. Here, a novel combination strategy utilizing carbon ion irradiation as a high-linear energy transfer (LET) radiotherapy and a thermo-triggered nanodevice is proposed, and drug accumulation in the tumor and treatment effects are evaluated using magnetic resonance imaging relaxometry and immunohistology (Ki-67, n = 15). The thermo-triggered liposomal anticancer nanodevice was administered into colon-26 tumor-grafted mice, and drug accumulation and efficacy was compared for 6 groups (n = 32) that received or did not receive the radiotherapy and thermo trigger.

Stereospecific Living Cationic Polymerization of -Vinylcarbazole through the Design of ZnCl-Derived Counteranions.

Highly stereospecific living polymerization of -vinylcarbazole (NVC) successfully proceeded via a cationic mechanism as a result of the elaborate design of counteranions using an initiating system consisting of CFSOH, BuNX (X = Cl, Br, I), and a Lewis acid catalyst. The use of ZnCl and an appropriate amount of BuNCl quantitatively generated highly isotactic polymers ( = 94%) with narrow molecular weight distributions (/ ∼ 1.3) and molecular weights proportional to monomer conversion.

Concurrent Cationic Vinyl-Addition and Coordination Ring-Opening Copolymerization via Orthogonal Propagation and Transient Merging at the Propagating Chain End.

Controlled cationic vinyl-addition polymerization of an alkyl vinyl ether (VE) and ring-opening polymerization of ε-caprolactone (CL) simultaneously proceeded using HfCl/Hf(OBu) as a dual-role catalyst for both mechanisms, yielding a graft copolymer consisting of a poly(VE) main chain and several poly(CL) side chains. The copolymer of conventionally incompatible monomers was generated via the unprecedented mechanisms consisting of orthogonal propagating reactions and transient merging. Specifically, the poly(CL) chains were incorporated into a poly(VE) chain through an exchange reaction between the VE-derived alkoxy group and the propagating poly(CL) chain at the acetal moiety of the propagating end of the poly(VE) chain.

Thermoactivatable polymer-grafted liposomes for low-invasive image-guided chemotherapy.

The objective of this study was to develop a thermotriggered, polymer-based liposomal drug carrier with an activatable magnetic resonance imaging (MRI) contrast property for monitoring the release of substances and for localized tumor therapy. The multimodal thermoactivatable polymer-grafted liposomes (MTPLs) were tested to investigate whether the accumulation of MTPLs in colon-26 grafted tumors could be visualized in vivo using MRI and optical imaging, whether MTPLs induce signal enhancement, reflecting the release of their contents, after triggering by short-term heating (42.5°C for 10 minutes) 9 hours after MTPL administration (late-phase triggering), and whether MTPLs can provide a sufficient antitumor effect.

Multifunctional liposomes having target specificity, temperature-triggered release, and near-infrared fluorescence imaging for tumor-specific chemotherapy.

We designed functional liposomes with target specificity, temperature-triggered drug release, and near-infrared fluorescence imaging. We prepared the liposomes by triple functionalization of stable pegylated liposomes with thermosensitive poly[2-(2-ethoxy)ethoxyethyl vinyl ether] chains (lower critical solution temperature around 38 °C) with conjugation of antibody trastuzumab (Herceptin, HER), which targets human epidermal growth factor 2, and with incorporation of indocyanine green for near-infrared fluorescence imaging. The liposomes retained DOX in the interior below physiological temperature but released DOX immediately at temperatures higher than 40 °C.

Exclusive One-Way Cycle Sequence Control in Cationic Terpolymerization of General-Purpose Monomers via Concurrent Vinyl-Addition, Ring-Opening, and Carbonyl-Addition Mechanisms.

Cationic terpolymerization of vinyl ether (VE), oxirane, and ketone successfully proceeded via unprecedented concurrent vinyl-addition, ring-opening, and carbonyl-addition mechanisms. In particular, the use of cyclohexene oxide as an oxirane resulted in terpolymerization via an exclusive one-way cycle, i.e.

Switchable dispersivity and molecular-trapping performance of mesostructured CaCO-thermosensitive polymer composite microspheres.

Monodispersed thermosensitive microspheres were synthesized by the combination of poly(N-isopropylacrylamide) (PNIPAAm) and a mesostructured framework consisting of vaterite CaCO nanocrystals ∼20 nm in diameter. The switchable dispersivity in water and organic media was provided to the rigid porous framework by the soft shell of the thermosensitive organic component. The microspheres were shuttlecocked between water and hydrophobic organic media by a swing in temperature across the lower critical solution temperature (LCST).

Evaluation of thermo-triggered drug release in intramuscular-transplanted tumors using thermosensitive polymer-modified liposomes and MRI.

Multi-modal thermo-sensitive polymer-modified liposomes (MTPLs) containing an anticancer drug, MR contrast agent, and fluorescent dye have been investigated as "theranostic" nanodevices that can be used to monitor drug delivery in cancer therapy. Here, we measured the physical characteristics of MTPLs, observed the dynamics of MTPLs in vivo, visualized heat-triggered drug release using MRI, and evaluated the treatment effects of the MTPLs with and without heating. In vitro experiments demonstrated that the MTPLs released drugs at temperatures above 41°C.

Effect of side-chain carbonyl groups on the interface of vinyl polymers with water.

The nature of the polymer-water interface in the poly(methyl 2-propenyl ether) (PMPE)-water model system is investigated by sum-frequency generation spectroscopy, which at the moment gives the best depth resolution among available techniques. PMPE, synthesized via living cationic polymerization, is structurally similar to poly(methyl methacrylate) (PMMA) except for lacking a carbonyl group. We here probe the polymer local conformation as well as the aggregation states of water at the interface.

Efficient Design for Stimuli-Responsive Polymers with Quantitative Acid-Degradability: Specifically Designed Alternating Controlled Cationic Copolymerization and Facile Complete Degradation.

Specifically designed alternating cationic copolymerization produced well-defined thermo- or pH-responsive polymers with complete acid-degradability. For example, a thermosensitive alternating copolymer with acid-labile acetal linkages in the main chain was obtained from the controlled cationic copolymerization of -methoxybenzaldehyde (pMeOBzA) and a vinyl ether (VE) with an oxyethylenic side chain. The resulting copolymer exhibited a sharp thermosensitive phase transition in water.

Concurrent cationic vinyl-addition and ring-opening copolymerization using B(C6F5)3 as a catalyst: copolymerization of vinyl ethers and isobutylene oxide via crossover propagation reactions.

Alkyl vinyl ethers and isobutylene oxide were concurrently copolymerized through cationic vinyl addition and ring opening using B(C6F5)3 as a catalyst. NMR analyses and acid hydrolysis of the products demonstrated that the copolymerization successfully proceeded through crossover reactions between vinyl and cyclic monomers to yield multiblock-like copolymers. Appropriate catalyst and monomer combinations with suitable reactivities were key for copolymerization.