Facile Fabrication of NIR-Responsive Alginate/CMC Hydrogels Derived through IEDDA Click Chemistry for Photothermal-Photodynamic Anti-Tumor Therapy.

Novel chemically cross-linked hydrogels derived from carboxymethyl cellulose (CMC) and alginate (Alg) were prepared through the utilization of the norbornene (Nb)-methyl tetrazine (mTz) click reaction. The hydrogels were designed to generate reactive oxygen species (ROS) from an NIR dye, indocyanine green (ICG), for combined photothermal and photodynamic therapy (PTT/PDT). The cross-linking reaction between Nb and mTz moieties occurred via an inverse electron-demand Diels-Alder chemistry under physiological conditions avoiding the need for a catalyst. The resulting hydrogels exhibited viscoelastic properties (G' ~ 492-270 Pa) and high porosity. The hydrogels were found to be injectable with tunable mechanical characteristics. The ROS production from the ICG-encapsulated hydrogels was confirmed by DPBF assays, indicating a photodynamic effect (with NIR irradiation at 1-2 W for 5-15 min). The temperature of the ICG-loaded hydrogels also increased upon the NIR irradiation to eradicate tumor cells photothermally. In vitro cytocompatibility assessments revealed the non-toxic nature of CMC-Nb and Alg-mTz towards HEK-293 cells. Furthermore, the ICG-loaded hydrogels effectively inhibited the metabolic activity of Hela cells after NIR exposure.

Fast Absorbent and Highly Bioorthogonal Hydrogels Developed by IEDDA Click Reaction for Drug Delivery Application.

In this work, we engineered highly biocompatible and fast absorbent injectable hydrogels derived from norbornene (Nb)-functionalized hyaluronic acid (HA-Nb) and a water-soluble cross-linker possessing tetrazine (Tz) functional groups on both ends of polyethylene glycol (PEG-DTz). The by-product (nitrogen gas) of the inverse electron demand Diels−Alder (IEDDA) cross-linking reaction carved porosity in the resulting hydrogels. By varying the molar ratio of HA-Nb and PEG-DTz (Nb:Tz = 10:10, 10:5, 10:2.5), we were able to formulate hydrogels with tunable porosity, gelation time, mechanical strength, and swelling ratios. The hydrogels formed quickly (gelation time < 100 s), offering a possibility to use them as an injectable drug delivery system. The experimental data showed rapid swelling and a high swelling ratio thanks to the existence of PEG chains and highly porous architectures of the hydrogels. The hydrogels were able to encapsulate a high amount of curcumin (~99%) and released the encapsulated curcumin in a temporal pattern. The PEG-DTz cross-linker, HA-Nb, and the resulting hydrogels showed no cytotoxicity in HEK-293 cells. These fast absorbent hydrogels with excellent biocompatibility fabricated from HA-Nb and the IEDDA click-able cross-linker could be promising drug carriers for injectable drug delivery applications.

Multi-stimuli responsive hydrogels derived from hyaluronic acid for cancer therapy application.

One of the most promising strategies for the controlled release of therapeutic molecules is stimuli-responsive and biodegradable hydrogels developed from natural polymers. However, current strategies to development stimuli-responsive hydrogels lack precise control over drug release profile and use cytotoxic materials during preparation. To address these issues, multi-stimuli responsive hydrogels derived from hyaluronic acid and diselenide based cross-linker were developed for the controlled release of doxorubicin (DOX). Hydrogels were rapidly formed via an inverse electron demand Diels-Alder click chemistry and encapsulated DOX/indocyanine green (ICG) in their porous networks. The hydrogels showed a rapid release of DOX in acidic (pH 5), reducing (10 mmol DTT), and oxidizing medium (0.5% H2O2), and after NIR irradiation. The in vitro experiments demonstrated that hydrogels were highly cytocompatible and the DOX-loaded hydrogels induced similar anti-tumor effect as compared to that of the free-DOX. Furthermore, DOX + ICG loaded hydrogels increased the antitumor efficacy of DOX after NIR irradiation.

Near-Infrared Light-Responsive Shell-Crosslinked Micelles of Poly(d,l-lactide)-b-poly((furfuryl methacrylate)-co-(N-acryloylmorpholine)) Prepared by Diels-Alder Reaction for the Triggered Release of Doxorubicin.

In the present study, we developed near-infrared (NIR)-responsive shell-crosslinked (SCL) micelles using the Diels-Alder (DA) click reaction between an amphiphilic copolymer poly(d,l-lactide)20-b-poly((furfuryl methacrylate)10-co-(N-acryloylmorpholine)78) (PLA20-b-P(FMA10-co-NAM78)) and a diselenide-containing crosslinker, bis(maleimidoethyl) 3,3'-diselanediyldipropionoate (BMEDSeDP). The PLA20-b-P(FMA10-co-NAM78) copolymer was synthesized by RAFT polymerization of FMA and NAM using a PLA20-macro-chain transfer agent (PLA20-CTA). The DA reaction between BMEDSeDP and the furfuryl moieties in the copolymeric micelles in water resulted in the formation of SCL micelles. The SCL micelles were analyzed by 1H-NMR, FE-SEM, and DLS. An anticancer drug, doxorubicin (DOX), and an NIR sensitizer, indocyanine green (ICG), were effectively incorporated into the SCL micelles during the crosslinking reaction. The DOX/ICG-loaded SCL micelles showed pH- and NIR-responsive drug release, where burst release was observed under NIR laser irradiation. The in vitro cytotoxicity analysis demonstrated that the SCL was not cytotoxic against normal HFF-1 cells, while DOX/ICG-loaded SCL micelles exhibited significant antitumor activity toward HeLa cells. Thus, the SCL micelles of PLA20-b-P(FMA10-co-NAM78) can be used as a potential delivery vehicle for the controlled drug release in cancer therapy.

Preparation of Doxorubicin-Loaded Amphiphilic Poly(D,L-Lactide-Co-Glycolide)-b-Poly(N-Acryloylmorpholine) AB2 Miktoarm Star Block Copolymers for Anticancer Drug Delivery.

Owing to their unique topology and physical properties, micelles based on miktoarm amphiphilic star block copolymers play an important role in the biomedical field for drug delivery. Herein, we developed a series of AB2-type poly(D,L-lactide-co-glycolide)-b-poly(N-acryloyl morpholine) (PLGA-b-PNAM2) miktoarm star block copolymers by reversible addition-fragmentation chain-transfer polymerization and ring-opening copolymerization. The resulting miktoarm star polymers were investigated by 1H NMR spectroscopy and gel permeation chromatography. The critical micellar concentration value of the micelles increases with an increase in PNAM block length. As revealed by transmission electron microscopy and dynamic light scattering, the amphiphilic miktoarm star block copolymers can self-assemble to form spherical micellar aggregates in water. The anticancer drug doxorubicin (DOX) was encapsulated by polymeric micelles; the drug-loading efficiency and drug-loading content of the DOX-loaded micelles were 81.7% and 9.1%, respectively. Acidic environments triggered the dissociation of the polymeric micelles, which led to the more release of DOX in pH 6.4 than pH 7.4. The amphiphilic PLGA-b-PNAM2 miktoarm star block copolymers may have broad application as nanocarriers for controlled drug delivery.

Diselenide Core Cross-Linked Micelles of Poly(Ethylene Oxide)-b-Poly(Glycidyl Methacrylate) Prepared through Alkyne-Azide Click Chemistry as a Near-Infrared Controlled Drug Delivery System.

In this article, a drug delivery system with a near-infrared (NIR) light-responsive feature was successfully prepared using a block copolymer poly(ethylene oxide)-b-poly(glycidyl methacrylate)-azide (PEO-b-PGMA-N3) and a cross-linker containing a Se-Se bond through "click" chemistry. Doxorubicin (DOX) was loaded into the core-cross-linked (CCL) micelles of the block copolymer along with indocyanine green (ICG) as a generator of reactive oxygen species (ROS). During NIR light exposure, ROS were generated by ICG and attacked the Se-Se bond of the cross-linker, leading to de-crosslinking of the CCL micelles. After NIR irradiation, the CCL micelles were continuously disrupted, which can be a good indication for effective drug release. Photothermal analysis showed that the temperature elevation during NIR exposure was negligible, thus safe for normal cells. In vitro drug release tests demonstrated that the drug release from diselenide CCL micelles could be controlled by NIR irradiation and affected by the acidity of the environment.

Triazine-based Polyelectrolyte as an Efficient Cathode Interfacial Material for Polymer Solar Cells.

A novel polyelectrolyte containing triazine (TAZ) and benzodithiophene (BDT) scaffolds with polar phosphine oxide (P═O) and quaternary ammonium ions as pendant groups, respectively, in the polymer backbone (PBTAZPOBr) was synthesized to use it as a cathode interfacial layer (CIL) for polymer solar cell (PSC) application. Owing to the high electron affinity of the TAZ unit and P═O group, PBTAZPOBr could behave as an effective electron transport material. Due to the polar quaternary ammonium and P═O groups, the interfacial dipole moment created by PBTAZPOBr substantially reduced the work function of the metal cathode to afford better energy alignment in the device, thus enabling electron extraction and reducing recombination of excitons at the photoactive layer/cathode interface. Consequently, the PSC devices based on the poly[4,8-bis(2-ethylhexyloxyl)benzo[1,2-b:4,5-b']dithiophene-2,6-diyl-alt-ethylhexyl-3-fluorothithieno[3,4-b]thiophene-2-carboxylate-4,6-diyl]:[6,6]-phenyl-C71-butyric acid methyl ester (PTB7:PC71BM) system with PBTAZPOBr as CIL displayed simultaneously enhanced open-circuit voltage, short-circuit current density, and fill factor, whereas the power conversion efficiency increased from 5.42% to 8.04% compared to that of the pristine Al device. The outstanding performance of PBTAZPOBr is attributed not only to the polar pendant groups of BDT unit but also to the TAZ unit linked with the P═O group of PBTAZPOBr, demonstrating that functionalized TAZ building blocks are very promising cathode interfacial materials (CIMs). The design strategy proposed in this work will be helpful to develop more efficient CIMs for high performance PSCs in the future.

Beta-Cyclodextrin Multi-Conjugated Magnetic Graphene Oxide as a Nano-Adsorbent for Methylene Blue Removal.

The composites of graphene oxide and magnetic nanoparticles multi-conjugated with beta-cyclodextrin (MNPs/GO-betaCD) were prepared by a facile route and their properties were investigated. First, poly(glycidyl methacrylate) was covalently wrapped onto the surface of magnetic nanoparticles (MNPs) by the reversible addition-fragmentation chain transfer polymerization. The mixture of modified MNPs and graphene oxide (GO) was then functionalized with beta-cyclodextrin to produce MNPs/GO-betaCD. The composites were characterized by FT-IR, XRD, TGA, SEM, and TEM. The MNPs/GO-betaCD owned a superparamagnetic character and showed remarkable methylene blue (MB) adsorption capacity from aqueous solution in comparison with GO. The adsorbent could be recycled and maintained about 64.4% of its initial adsorption capacity for MB after five regeneration cycles.

Synthesis and Properties of an Ionic Conjugated Polymer via the Uncatalyzed Polymerization of 2-Ethynylpyridine Using Bromocholine Bromide.

A new ionic polyacetylene was synthesized via the uncatalyzed polymerization of 2-ethynylpyridine using bromocholine bromide in high yield. The activated acetylenic triple bond of N-bromocholine-2-ethynylpyridinium bromide, formed at first quaternarization process, was found to be susceptible to linear polymerization. The polymer structure was characterized by various instrumental methods to have the polyacetylene backbone structure with the designed substituent. The inherent viscosities of the resulting polymers were in the range of 0.10-0.15 dL/g and X-ray diffraction analysis data indicated that this polymer is mostly amorphous. The electro-optical and electrochemical properties were measured and discussed. The polymer exhibited the irreversible electrochemical behaviors between the doping and undoping peaks.

Fabrication of Phenanthroline Modified Graphene Nanosheets Decorated with Palladium Nanoparticles.

Palladium nanoparticles decorated modified reduced graphene oxide (RGO) composite was synthesized by a two-step process using 1,10-Phenanthroline (PHEN) as bridging agent. Firstly, the graphene oxide (GO) was non-covalently modified with the PHEN molecules through π-π interaction between two components. Then, the modified GO was complexed with Pd precursor and subsequently reduced from Pd2+ to Pd0 using NaBH4 to yield Pd dispersed modified RGO sheets. The structure and morphology of the resulting composites were characterized by FTIR, TGA, EDX, FESEM, HRTEM and XRD measurements. XPS results revealed that the reduction of Pd2+ to metal-lic Pd was successfully achieved, while the HRTEM and FESEM micrographs suggested that the Pd nanoparticles were well-dispersed on the functionalized graphene sheets.

Covalent Incorporation of SiO2 Nanoparticles in CO2-Based Copolymers: Synthesis, Characterization, Morphology and Property Studies.

A new strategy has been developed for covalent incorporation of SiO2 nanoparticles (N-'s) in the CO2-based copolymer, poly(propylene carbonate-co-propylene oxide) (poly(PC-co-PO)). The poly(PC-co-PO)-g-SiO2 nanocomposites was prepared by the combination of epoxy-CO2 ring-opening polymerization and the condensation reaction of chloride and hydroxyl groups of the polymer and the SiO2 surface. FT-IR and NMR were employed for the characterization of the copolymers as well as nanocomposites. A uniform and spherical core-shell structure of poly(PC-co-PO)-g-SiO2 nanocomposites was demonstrated from TEM and SEM images. An improved thermal property of the polymer matrix with incorporating SiO2 nanoparticles was revealed by TGA study. The grafting of poly(PC-co-PO) considerably prevented the aggregation and improved the dispersibility of SiO2 nanoparticles in toluene.

Uncatalyzed synthesis and characterization of a water-soluble polyacetylene: poly[2-ethynyl-N-(propylsulfonate)pyridinium betaine].

A new ionic conjugated polymer was prepared by the activated polymerization of 2-ethynylpyridine with the ring-opening of 1,3-propanesultone without any additional initiator or catalyst. This polymer was characterized by various instrumental methods to have conjugated polymer backbone system with pendant N-propylsulfonate functional groups. The photoluminescence spectrum of polymer showed that the PL peak is located at 552 nm corresponding to the photon energy of 2.25 eV. The cyclovoltammograms of polymer exhibited the irreversible electrochemical behaviors between the oxidation and reduction peaks. The oxidation current density of polymer versus the scan rates is approximately linear relationship in the range of 30-120 mV/sec. It was found that the kinetics of the redox process is almost controlled by the reactant diffusion process from the oxidation current density of polymer versus the scan rates.

Synthesis and characterization of phenylpyridine-based iridium(III) complex for solution-processed phosphorescent organic light-emitting diode.

A novel main ligand 2-(2,4-dimethoxyphenyl)-5-trifluoromethylpyridine (MeO2CF3ppy) and its complex bis[2-(2,4-dimethoxy-phenyl)-5-trifluoromethyl pyridinato-N,C2]iridium acetylacetonate (MeO2CF3ppy)2Ir(acac) was synthesized. 2,4-Dimethoxy and 5-trifluoromethyl group were incorporated into main ligand to tune luminescence color. The phosphorescence organic light-emitting diodes (PhOLEDs) based on this complex with the configuration of ITO/PEDOT:PSS (40 nm)/PVK:CBP:Ir(III) complex (50 nm)/BCP (20 nm)/LiF (0.7 nm)/Al (100 nm) were fabricated. The solution-processed PhOLEDs based on (MeO2CF3ppy)2Ir(acac) exhibited a maximum quantum efficiency of 4.18% and luminance efficiency 9.04 cd/A with CIE coordinate of (0.32, 0.64).

Synthesis and properties of an ionic conducting material: in-situ preparation of poly(2-ethynyl-N-iodopyridinium iodide) and its electro-optical and electrochemical properties.

Poly(2-ethynyl-N-iodopyridinium iodide) [PEIPI] was easily prepared via in-situ uncatalyzed polymerization of 2-ethynylpyridine by using iodine. The activated acetylenic bond of 2-ethynyl-N-iodopyridinium iodide formed at the initial reaction time was assumed to be susceptible to linear polymerization, followed by an identical propagation step that contains the produced macroanion and quaternized monomeric species. The polymer structure was characterized by various instrumental methods to have the conjugated polymer backbone system bearing the designed substituents. The electro-optical and electrochemical properties of polymer were studied. The UV-visible spectrum of PEIPI showed a characteristic absorption peak in the visible region up to 800 nm. The PL emission spectrum of PEIPI shows two peaks at 515 and 550 nm. The cyclic voltammetry of PEIPI exhibited irreversible electrochemical behavior between the oxidation and reduction peaks.

Synthesis and characterization of an ionic conjugated polymer: poly[2-ethynyl-N-(2-furoyl)pyridinium chloride].

A new ionic polyacetylene derivative with furoyl substituents was prepared by the uncatalyzed polymerization of 2-ethynylpyridine by using 2-furoyl chloride in high yield. The polymer structure was characterized by such instrumental methods as NMR, IR, and UV-visible spectroscopies to have a polyacetylene backbone system with the N-(2-furoyl)pyridinium chloride. The electro-optical and electrochemical properties of poly[2-ethynyl-N-(2-furoyl)pyridinium chloride [PEFPC] were studied. The photoluminescence spectrum showed that the PL peak is at 578 nm corresponding to the photon energy of 2.15 eV. The cyclovoltammograms of PEFPC exhibited the irreversible electrochemical behaviors between the oxidation and reduction peaks. The oxidation current density of polymer versus the scan rates is approximately linear relationship in the range of 30 mV/sec-150 mV/sec. It was found that the kinetics of redox process is controlled by the reactant diffusion process from the oxidation current density of PEFPC versus the scan rates.

Noncovalent grafting of poly(3-octylthiophene) at the edges of the graphene nanosheets.

Noncovalent functionalization of graphene was carried out via in-situ oxidative polymerization of poly(3-octylthiophene) (P3OT). First, graphene sheets were prepared by a modified Hummer's method and subsequently reduced with hydrazine monohydrate. The structure and morphology of the composites were investigated by using FTIR, XPS, EDX, TGA, HRTEM, FESEM and XRD measuments. The results obtained from spectroscopic studies confirm the reduction of graphite oxide to graphene. UV-Vis and photoluminescence spectroscopies were also used to prove the doping function of the graphene in the composites. Dispersion stability indicates the good mixing between graphene and the polymer due to pi-pi interaction between two components. Scanning electron microscopy results suggest that the graphene sheets were well dispersed in the polymer matrix. The UV-Vis spectra of graphene/P3OT composites show a red shift by a few nanometers, while the emission spectra show a small blue shift. However, the nanocomposites retained the photoluminescence property of as synthesized P3OT.

Preparation and characterization of graphene/poly(diphenylamine) composites.

Nanocomposites of graphene nanosheets and poly(diphenylamine) (graphene-PDPA) were synthesized via the in-situ oxidative polymerization of diphenylamine in a sulphuric acid medium. First, graphite oxide (GO) was prepared by oxidation of natural graphite using the modified Hummer's method and subsequently reduced using hydrazine monohydrate. The as-prepared graphene sheets were noncovalently grafted with PDPA using ammonium peroxydisulphate as an oxidant. During the polymerization, graphene sheets were homogeneously dispersed in the PDPA matrix. The formation of the hybrid material was confirmed by FTIR, XPS, TGA, HRTEM, FESEM and XRD measurements. XPS analysis revealed the removal of oxygen functionality from the GO surface after reduction and the bonding structure of the reduced hybrids. In addition, the nanocomposites showed better thermal properties due to the intrinsic property of the graphene sheets.

Fabrication and characterization of graphene/poly(p-phenylenediamine) hybrids.

Graphene nanosheets functionalized with poly(p-phenylenediamine) (PPDA) were prepared via the in-situ chemical oxidative polymerization using potassium persulphate as a catalyst. Graphene nanosheets were previously prepared by chemical reduction of exfoliated graphite oxide. The structure and morphology of the composite material were characterized by FTIR, XPS, HRTEM, FESEM and XRD, while the thermal and electrical properties were measured by TGA and a four-probe method. FESEM and HRTEM observations indicated that the graphene sheets were encapsulated in the PPDA matrix. Furthermore, the nanocomposites exhibited improved conductivity and thermal stability as compared with pure PPDA.

Chemical modification of polyhedral oligomeric silsesquioxanes by functional polymer via azide-alkyne click reaction.

A series of poly(methylmethacrylate-co-2-hydroxyethylmethacrylate)/polyhedral oligomeric silsesquioxanes (P(MMA-co-HEMA)/POSS) nanocomposites were synthesized by the combination of ATRP and click chemistry. The hybrid nanocomposites were characterized by FT-IR, 1H-NMR, GPC, SEM, XRD, DSC, and TGA analyses. The loading of POSS in the nanocomposites was calculated using 1H-NMR data. TGA measurements suggested that the incorporation of POSS into polymer matrices enhanced decomposition temperature as well as char yield of the polymeric materials. The glass transition temperature linearly increased with the increase of POSS loading plausibly because of the aggregation of POSS nanoparticles and the dipole-dipole interaction between POSS and P(MMA-co-HEMA) segments.

Synthesis and characterization of TiO2/poly(methyl methacrylate) nanocomposites via surface thiol-lactam initiated radical polymerization.

An approach to the surface modification of TiO2 nanoparticles was described based on the thiol functionalization of TiO2 followed by thiol-lactam initiated radical polymerization (TLIRP) of methyl methacrylate (MMA). FT-IR, XRD and XPS analyses confirmed the grafting of the polymer on the TiO2 surface. TGA analysis revealed superior thermal stability of PMMA-g-TiO2 compared with PMMA. TEM measurements and time-dependent phase monitoring suggested much higher colloidal stability of PMMA-g-TiO2 than TiO2 in toluene. The controlled nature of the TLIRP of MMA from the surface of TiO2 was determined by GPC analysis.