Heparin bioconjugate with a thermoresponsive cationic branched polymer: a novel aqueous antithrombogenic coating material

With a view to reducing the thrombogenic potential of artificial blood-contact devices and natural tissues, we developed a novel aqueous antithrombogenic coating material, comprising a heparin bioconjugate that incorporated a thermoresponsive cationic polymer as a surfactant. The polymer was prepared by the sequential steps of initiator-transfer agent-terminator (iniferter)-based living radical photopolymerization of N-[3-(dimethylamino)propyl]acrylamide, followed by the polymerization of N-isopropylacrylamide from tetra(N,N-diethyldithiocarbamylmethyl)benzene as a multifunctional iniferter. The polymer obtained possessed four branched chains, each consisting of a cationic PDMAPAAm block (Mn: ca. 3000 g.mol(-1)) forming an inner domain for heparin binding and a thermoresponsive PNIPAM block (Mn: ca. 6000 g.mol(-1)) forming an outer domain for surface fixation; bioconjugation of the polymer with heparin occurred immediately upon simple mixing in an aqueous medium. Because the lower critical solution temperature of the heparin bioconjugate was approximately 35 degrees C, it could be coated from an aqueous solution at room temperature. The excellent adsorptivity and high durability of the coating below 37 degrees C was demonstrated on several generally used polymers by wettability measurement and surface chemical compositional analysis, and on collagen sheets and rat skin tissue by heparin staining. Blood coagulation was significantly prevented on the heparin bioconjugate-coated surfaces. The thermoresponsive bioconjugate developed therefore appeared to satisfy the initial requirements for a biocompatible aqueous coating material.     

Synthesis and self‐assembly of thermoresponsive block‐graft fluoropolymer as well as its tunable wettability surface

Thermo‐responsive block‐graft fluoropolymer is synthesized and investigated the self‐assembly morphology and the tunable wettability surface on cotton fabric by dip‐coating into the micelles with different temperatures. Well‐defined block‐graft copolymer is prepared by click chemistry with poly(hexafluorobutyl methacrylate)‐block‐poly(glycidyl methacrylate) (PHFBMA‐b‐PGMA) and homopolymer poly(N‐isopropylacrylate) with alkyne on main chain (Alkynyl‐PNIPAM) to synthesize final block‐graft polymer PHFBMA‐b‐(PGMA‐g‐PNIPAM). The thermo‐responsive behaviors of block‐graft polymer prove that the diameter for fluoropolymer micelle is about 50–70 nm with uniform sphere shape at room temperature and bigger and broader at 40 °C. The surface of cotton fabric processed in micelle solution at room temperature is smooth and has good hydrophobic property, while it has the hydrophilic property dipped in high temperature micelle solution. This work may give valuable guidance for fabricating a facile strategy to establish controllable wettability surfaces on different substrates, which is a promising candidate for the coating materials and industrial fields. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 992–1002     

Controlled nitroxide-mediated styrene surface graft polymerization with atmospheric plasma surface activation

Polymer layer growth by free radical graft polymerization (FRGP) and controlled nitroxide-mediated graft polymerization (NMGP) of polystyrene was achieved by atmospheric pressure hydrogen plasma surface activation of silicon. Kinetic polystyrene layer growth by atmospheric pressure plasma-induced FRGP (APPI-FRGP) exhibited a maximum surface-grafted layer thickness (125 A after 20 h) at an initial monomer concentration of [M] 0 = 2.62 M at 85 degrees C. Increasing both the reaction temperature ( T = 100 degrees C) and initial monomer concentration ([M] 0 = 4.36 M) led to an increased initial film growth rate but a reduced polymer layer thickness, due to uncontrolled thermal initiation and polymer grafting from solution. Controlled atmospheric pressure plasma-induced NMGP (APPI-NMGP), using 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), exhibited a linear increase in grafted polystyrene layer growth with time due to controlled surface graft polymerization as well as reduced uncontrolled solution polymerization and polymer grafting, resulting in a polymer layer thickness of 285 A after 60 h at [TEMPO] = 10 mM, [M] 0 = 4.36 M, and T = 120 degrees C. Atomic force microscopy (AFM) surface analysis demonstrated that polystyrene-grafted surfaces created by APPI-NMGP exhibited a high surface density of spatially homogeneous polymer features with a low root-mean-square (RMS) surface roughness ( R rms = 0.36 nm), similar to that of the native silicon surface ( R rms = 0.21 nm). In contrast, polymer films created by APPI-FRGP at [M] 0 = 2.62 M demonstrated an increase in polymer film surface roughness observed at reaction temperatures of 85 degrees C ( R rms = 0.55 nm) and 100 degrees C ( R rms = 1.70 nm). The present study concluded that the current approach to APPI controlled radical polymerization may be used to achieve a grafted polymer layer with a lower surface roughness and a higher fractional coverage of surface-grafted polymers compared to both conventional FRGP and APPI-FRGP.     

Thermoresponsive poly(N-isopropylacrylamide) copolymers: contact angles and surface energies of polymer films

Surface properties of poly(N-isopropylacrylamide) (PNIPAM) copolymer films were studied by contact angle measurements and optical and atomic force microscopy. We prepared a series of copolymers of N-isopropylacrylamide with N-tert-butylacrylamide (NtBA) in order of increasing hydrophobicity. The measurements of the advancing contact angle of water at 37 degrees C were hampered by the observation of a distinct stick/slip pattern on all polymers in the series with the exception of poly(NtBA) (PNtBA). We attributed this behavior to the film deformation by the vertical component of liquid surface tension leading to the pinning of the moving contact line. This was confirmed by the observation of a ridge formed at the pinned contact line by optical microscopy. However, meaningful contact (without the stick/slip pattern and with a time-independent advancing contact angle) angles for this thermoresponsive polymer series could be obtained with carefully selected organic liquids. We used the Li and Neumann equation of state to calculate the surface energy and contact angles of water for all polymers in the series of copolymers and van Oss, Chaudhury, and Good (vOCG) acid-base theory for PNtBA. The surface energies of the thermoresponsive polymers were in the range of 38.9 mJ/m2 (PNIPAM) to 31 mJ/m2 (PNtBA) from the equation of state approach. The surface energy of PNtBA calculated using vOCG theory was 29.0 mJ/m2. The calculated contact angle for PNIPAM (74.5 +/- 0.2 degrees ) is compared with previously reported contact angles obtained for PNIPAM-modified surfaces.     

Effect of structural isomerism and polymer end group on the pH-stability of hydrogen-bonded multilayers

Association of tannic acid (TA) with structurally isomeric poly(N-isopropylacrylamide) (PNIPAM) and poly(2-isopropyl-2-oxazoline) (PIPOX) has been examined at surfaces to understand the effect of different molecular arrangements in a polymer repeating unit of structural isomers on the construction and pH-stability of hydrogen-bonded multilayers. Films were fabricated using layer-by-layer (LbL) technique through hydrogen-bonding interactions primarily between carbonyl groups of neutral polymers and hydroxyl groups of TA molecules at pH 2. PIPOX and TA formed thinner and more stable films in the pH scale with a critical dissolution pH of 9 when compared to films of PNIPAM and TA with a critical pH of 8. The differences in the thickness and pH-stability were due to different conformational behavior of PNIPAM and PIPOX in water which affects the accessibility of carbonyl groups for participation in the hydrogen bonding and the number of binding sites between the polymer pairs. Addition of electrostatic interactions by introducing amino groups only at the PIPOX chain end shifted the critical dissolution pH to higher values and resulted in gradual dissolution of the films in a wide pH range of 9-12. Such films hold promise for use in biomedical field due to biocompatibility and lower critical solution temperature (LCST) behavior at near physiological temperature of PNIPAM and PIPOX together with the pH-response of the hydrogen-bonded films.     

Iniferter concept and living radical polymerization

Iniferters are initiators that induce radical polymerization that proceeds via initiation, propagation, primary radical termination, and transfer to initiator. Because bimolecular termination and other transfer reactions are negligible, these polymerizations are performed by the insertion of the monomer molecules into the iniferter bond, leading to polymers with two iniferter fragments at the chain ends. The use of well‐designed iniferters would give polymers or oligomers bearing controlled end groups. If the end groups of the polymers obtained by a suitable iniferter serve further as a polymeric iniferter, these polymerizations proceed by a living radical polymerization mechanism in a homogeneous system. In these cases, the iniferters (C S bond) are considered a dormant species of the initiating and propagating radicals. In this article, I describe the history, ideas, and some characteristics of iniferters and living radical polymerization with some iniferters that contain dithiocarbamate groups as photoiniferters and several compounds as thermal iniferters. From the viewpoint of controlled polymer synthesis, iniferters can be classified into several types: thermal or photoiniferters; monomeric, polymeric, or gel iniferters; monofunctional, difunctional, trifunctional, or polyfunctional iniferters; monomer or macromonomer iniferters; and so forth. These lead to the synthesis of various monofunctional, telechelic, block, graft, star, and crosslinked polymers. The relations between this work and other recent studies are discussed. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 2121–2136, 2000     

Salt effect on the heat-induced association behavior of gold nanoparticles coated with poly(N-isopropylacrylamide) prepared via reversible addition-fragmentation chain transfer (RAFT) radical polymerization

Poly(N-isopropylacrylamide) (PNIPAM) with a narrow molecular weight distribution was prepared by reversible addition-fragmentation chain transfer (RAFT) radical polymerization. A dithioester group at the chain end of PNIPAM thus prepared was cleaved by treating with 2-ethanolamine to provide thiol-terminated PNIPAM with which gold nanoparticles were coated via reactions of the terminal thiol with gold. The thermoresponsive nature of the maximum wavelength of the surface plasmon band and hydrodynamic radius (Rh) for the PNIPAM-coated gold nanoparticles were found to be sensitively affected by added salt. In pure water, Rh for the PNIPAM-coated gold nanoparticles at 40 degrees C (>lower critical solution temperature (LCST)) was smaller than that at 25 degrees C (相似文献   

Ultrathin poly(N-isopropylacrylamide) grafted layer on polystyrene surfaces for cell adhesion/detachment control

We investigated physicochemical properties of two types of poly(N-isopropylacrylamide) (PIPAAm)-grafted tissue culture polystyrene (TCPS) surfaces, to elucidate the influential factors for thermally regulated cell adhesion and detachment to PIPAAm-grafted surfaces. The two types of PIPAAm-grafted surfaces were prepared by the electron beam polymerization method. Attenuated total reflection Fourier transform infrared spectroscopy revealed that amounts of the grafted polymers were 1.4 +/- 0.1 microg/cm2 for PIPAAm-1.4 and 2.9 +/- 0.1 microg/cm2 for PIPAAm-2.9. Both PIPAAm-grafted surfaces showed hydrophobic/hydrophilic property alterations in response to temperature. However, PIPAAm-1.4 surfaces were more hydrophobic (cos theta = 0.21 at 37 degrees C and cos theta = 0.35 at 20 degrees C) than PIPAAm-2.9 (cos theta = 0.42 at 37 degrees C and cos theta = 0.50 at 20 degrees C) both above and below the PIPAAm's transition temperature. Thicknesses of the grafted PIPAAm layers were estimated to be 15.5 +/- 7.2 nm for PIPAAm-1.4 and 29.5 +/- 8.4 nm for PIPAAm-2.9, by the use of UV excimer laser and atomic force microscope. Bovine carotid artery endothelial cells (ECs) adhere to the surfaces of PIPAAm-1.4 and proliferate to form confluent cell monolayers. The cell monolayers were harvested as single cell sheets by temperature decrease from 37 to 20 degrees C. On the contrary, ECs did not adhere to the surfaces of PIPAAm-2.9. This phenomenon was correlated with an adsorption of cell adhesion protein, fibronectin, onto surfaces ofPIPAAm-1.4 and -2.9. In the case of nano-ordered thin grafted surfaces, the surface chain mobility is strongly influenced by the thickness of PIPAAm grafted layers because dehydration of PIPAAm chains should be enhanced by the hydrophobic TCPS surfaces. PIPAAm graft amounts, that is, thickness of the PIPAAm grafted layers, play a crucial role in temperature-induced hydrophilic/hydrophobic property alterations and cell adhesion/detachment behavior.     

Patterning on nonplanar substrates: flexible honeycomb films from a range of self-assembling star copolymers

The effect of glass transition temperature, Tg, on the self-assembly of "honeycomb" microstructures on nonplanar substrates was probed by the synthesis of a library of core cross-linked star polymers with different arm compositions. Star polymers based on poly(dimethyl siloxane), poly(ethyl acrylate), poly(methyl acrylate), poly(tert-butyl acrylate), and poly(methyl methacrylate) were synthesized by the "arm first" strategy using atom-transfer radical polymerization. Reaction conditions were optimized, and a series of high molecular weight star polymers were prepared in high yield. The glass transition temperature of the star polymers ranged from -123 to 100 degrees C which allowed the suitability for the formation of porous honeycomb-like films via the "breath figure" technique on nonplanar surfaces to be investigated. All star compositions successfully formed ordered films on flat surfaces. However, only star polymer compositions with a Tg below 48 degrees C could form homogeneous honeycomb coatings on the surface of nonplanar substrates.     

Grafting acrylic polymers from flat nickel and copper surfaces by surface-initiated atom transfer radical polymerization

Acrylic polymers, including poly(methyl methacrylate), poly(2,2,2-trifluoroethyl methacrylate), poly( N,N'-dimethyaminoethyl methacrylate), and poly(2-hydroxyethyl methacrylate) were grafted from flat nickel and copper surfaces through surface-initiated atom transfer radical polymerization (ATRP). For the nickel system, there was a linear relationship between polymer layer thickness and monomer conversion or molecular weight of "free" polymers. The thickness of the polymer brush films was greater than 80 nm after 6 h of reaction time. The grafting density was estimated to be 0.40 chains/nm2. The "living" chain ends of grafted polymers were still active and initiated the growth of a second block of polymer. Block copolymer brushes with different block sequences were successfully prepared. The experimental surface chemical compositions as measured by X-ray photoelectron spectroscopy agreed very well with their theoretical values. Water contact angle measurements further confirmed the successful grafting of polymers from nickel and copper surfaces. The surface morphologies of all samples were studied by atomic force microscopy. This study provided a novel approach to prepare stable functional polymer coatings on reactive metal surfaces.     

Endgroup analysis of isolated poly(methyl methacrylate) from graft copolymers of wool

In order to elucidate the termination mechanism in the graft copolymerization of methyl methacrylate to unreduced and reduced wool fibers, graft copolymers were prepared by means of the LiBr–K₂S₂O₈ redox sytem without homopolymer or with K₂S₂O₈ only with homopolymer at 30°C. The graft polymers (PMMA) were isolated almost completely from the wool trunk by an HCI-digestion method, leaving a few amino acid residues on the end of the graft polymers. Dinitrophenylation of the isolated polymer was carried out by various methods. The spectral features were almost the same as for dinitrophenylated amino acids of the usual type such as valine, leucine, and methionine, with a maximum in ultraviolet light at 340–345 mμ. From colorimetric analysis of the number of dinitrophenylated amino acid endgroups and the measurement of the average molecular weight of the isolated polymers, the number of amino acid endgroups linked to the graft polymers was calculated to be about one and two per polymer chain in reduced and unreduced wool, respectively, independent of the reaction system, graft-on, and molecular weight of graft polymers. From these facts, it was suggested that the most of isolated polymers are the truly grafted polymers. Also, the termination reactions have been explained as follows. In the unreduced wool, the restriction of mobility of the radical end might be expected, for the confinement of growing chains in wool fibers. This would be favorable to termination by recombination rather than by the disproportionation, since the former has a lower activation energy than the latter. Thus, the formation of intra- or intermolecular crosslinks might be considered between polypeptide chains. On the other hand, in the reduced wool, the mobility of graft polymers might be considered to be greater than that of unreduced wool because of its open structure. Therefore, termination would be principally by disproportionation between graft polymer radicals.     

Functionalization of hydrogen-terminated silicon via surface-initiated atom-transfer radical polymerization and derivatization of the polymer brushes

Surface-initiated atom-transfer radical polymerization (ATRP) of poly(ethylene glycol) monomethacrylate (PEGMA) was carried out on the hydrogen-terminated Si(100) substrates with surface-tethered alpha-bromoester initiator. Kinetic studies confirmed an approximately linear increase in polymer film thickness with reaction time, indicating that chain growth from the surface was a controlled "living" process. The "living" character of the surface-grafted PEGMA chains was further ascertained by the subsequent extension of these graft chains, and thus the graft layer. Well-defined polymer brushes of near 100 nm in thickness were grafted on the Si(100) surface in 8 h under ambient temperature in an aqueous medium. The hydroxyl end groups of the poly(ethylene glycol) (PEG) side chains of the grafted PEGMA polymer were derivatized into various functional groups, including chloride, amine, aldehyde, and carboxylic acid groups. The surface-functionalized silicon substrates were characterized by reflectance FT-IR spectroscopy and X-ray photoelectron spectroscopy (XPS). Covalent attachment and derivatization of the well-defined PEGMA polymer brushes can broaden considerably the functionality of single-crystal silicon surfaces.     

End-grafted low-molecular-weight PNIPAM does not collapse above the LCST

The interfacial properties of end-grafted temperature-responsive poly(N-isopropylacryamide) (PNIPAM) were quantified by direct force measurements both above and below the lower critical solution temperature (LCST) of 32 degrees C. The forces were measured between identical, opposing PNIPAM films and between a PNIPAM film and a lipid membrane. At the grafting densities and molecular weights investigated, the polymer extension did not change significantly above the LCST, and the polymers did not adhere. Below the LCST, the force-distance profiles suggest a vertical phase separation, which results in a diluter outer layer and a dense surface proximal layer. At large separations, the force profiles agree qualitatively with simple polymer theory but deviate at small separations. Importantly, at these low grafting densities and molecular weights, the end-grafted PNIPAM does not collapse above the LCST. This finding has direct implications for triggering liposomal drug release with end-grafted PNIPAM, but it increases the temperature range where these short PNIPAM chains function as steric stabilizers.     

Effect of chain density and conformation on protein adsorption at PEG-grafted polyurethane surfaces

Polyurethanes were modified using monobenzyloxy polyethylene glycol (BPEG) which possesses a bulky hydrophobic benzyloxy group at one end and a hydroxyl group at the other end as a preconstructed BPEG layer, and poly(ethylene glycol) (PEG) and monomethoxyl poly(ethylene glycol) (MPEG) with various chain lengths as fillers. Our objective was to investigate the effect of PEG graft density and conformation on protein adsorption at PEGlated surface. The graft density was estimated by a chemical titration method. The combination of ATR-FTIR, AFM and titration results provide evidences that the graft density can be increased by backfilling PEG or MPEG to a BPEG layer. However, fibrinogen and albumin adsorption significantly increased on all surfaces after PEG or MPEG backfilling. We conclude that the conformation of hydrophobic benzyloxy end groups of the BPEG layer plays a key role. The benzyloxy end groups of preconstructed PEG chains stretch to the surface after PEG backfilling, which possibly accounts for the observed increase in protein adsorption. The BPEG conformation change after backfilling with PEG or MPEG was also suggested by contact angles. Additionally, protein adsorption was slightly influenced by the length of filler, suggesting a change in surface morphology.     

Phase transition behavior of unimolecular micelles with thermoresponsive poly(N-isopropylacrylamide) coronas

This paper describes the double phase transition behavior of a thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) brush at the surface of a hydrophobic core. Reversible addition-fragmentation transfer (RAFT) polymerization of N-isopropylacrylamide (NIPAM) was conducted by using a hyperbranched polyester (Boltorn H40) based macroRAFT agent. The resultant multiarm star block copolymer (H40-PNIPAM) exists as unimolecular micelles with hydrophobic H40 as the core, densely grafted PNIPAM brush as the shell. A combination of laser light scattering (LLS) and microdifferential scanning calorimetry (micro-DSC) studies of H40-PNIPAM in aqueous solution reveals double phase transitions of the PNIPAM corona, which is in contrast to the fact that free PNIPAM homopolymer in aqueous solution exhibits a lower critical solution temperature (LCST) at approximately 32 degrees C. The first phase transition takes place in the broad temperature range 20-30 degrees C, which can be tentatively ascribed to the n-cluster-induced collapse of the inner region of the PNIPAM brush close to the H40 core; the second phase transition occurs above 30 degrees C, which can be ascribed to the outer region of PNIPAM brush. Employing the RAFT chain extension technique, the inner and outer part of PNIPAM brush were then selectively labeled with pyrene derivatives, respectively; temperature-dependent excimer fluorescence measurements further support the conclusion that the inner part of PNIPAM brush collapses first at lower temperatures, followed by the collapse of the outer part at higher temperatures.     

Protein adhesion on silicon-supported hyperbranched poly(ethylene glycol) and poly(allylamine) thin films

Hyperbranching poly(allylamine) (PAAm) and poly(ethylene glycol) (PEG) on silicon and its effect on protein adhesion was investigated. Hyperbranching involves sequential grafting of polymers on a surface with one of the components having multiple reactive sites. In this research, PAAm provided multiple amines for grafting PEG diacrylate. Current methodologies for generating PEG surfaces include PEG-silane monolayers or polymerized PEG networks. Hyperbranching combines the nanoscale thickness of monolayers with the surface coverage afforded by polymerization. A multistep approach was used to generate the silicon-supported hyperbranched polymers. The silicon wafer surface was initially modified with a vinyl silane followed by oxidation of the terminal vinyl group to present an acid function. Carbodiimide activation of the surface carboxyl group allowed for coupling to PAAm amines to form the first polymer layer. The polymers were hyperbranched by grafting alternating PEG and PAAm layers to the surface using Michael addition chemistry. The alternating polymers were grafted up to six total layers. The substrates remained hydrophilic after each modification. Static contact angles for PAAm (32-44 degrees) and PEG (33-37 degrees) were characteristic of the corresponding individual polymer (30-50 degrees for allylamine, 34-42 degrees for PEG). Roughness values varied from approximately 1 to 8 nm, but had no apparent affect on protein adhesion. Modifications terminating with a PEG layer reduced bovine serum albumin adhesion to the surface by approximately 80% as determined by ELISA and radiolabel binding studies. The hyperbranched PAAm and PEG surfaces described in this paper are nanometer-scale, multilayer films capable of reducing protein adhesion.     

Thermo-induced formation of unimolecular and multimolecular micelles from novel double hydrophilic multiblock copolymers of N,N-dimethylacrylamide and N-isopropylacrylamide

Two novel double hydrophilic multiblock copolymers of N,N-dimethylacrylamide and N-isopropylacrylamide, m-PDMAp-PNIPAMq, with varying degrees of polymerization (DPs) for PDMA and PNIPAM sequences (p and q) were synthesized via consecutive reversible addition-fragmentation chain transfer (RAFT) polymerizations using polytrithiocarbonate (1) as the chain transfer agent (Scheme 1), where PDMA is poly(N,N-dimethylacrylamide) and PNIPAM is poly(N-isopropylacrylamide). The DPs of PDMA and PNIPAM sequences were determined by 1H NMR, and the block numbers, i.e., number of PDMAp-PNIPAMq sequences (n), were obtained by comparing the molecular weights of multiblock copolymers to that of cleaved products as determined by gel permeation chromatography (GPC). m-PDMA42-PNIPAM37 and m-PDMA105-PNIPAM106 multiblock copolymers possess number-average molecular weights (Mn) of 4.62x10(4) and 9.53x10(4), respectively, and the polydispersities (Mw/Mn) are typically around 1.5. Block numbers of the obtained multiblock copolymers are ca. 4, which are considerably lower than the numbers of trithiocarbonate moieties per chain of 1 (approximately 20) and m-PDMAp precursors (approximately 6-7). PDMA homopolymer is water soluble to 100 degrees C, while PNIPAM has been well known to exhibit a lower critical solution temperature (LCST) at ca. 32 degrees C. In aqueous solution, m-PDMA42-PNIPAM37 and m-PDMA105-PNIPAM106 multiblock copolymers molecularly dissolve at room temperature, and their thermo-induced collapse and aggregation properties were characterized in detail by a combination of optical transmittance, fluorescence probe measurements, laser light scattering (LLS), and micro-differential scanning calorimetry (micro-DSC). It was found that chain lengths of PDMA and PNIPAM sequences exert dramatic effects on their aggregation behavior. m-PDMA105-PNIPAM106 multiblock copolymer behaves as protein-like polymers and exhibits intramolecular collapse upon heating, forming unimolecular flower-like micelles above the thermal phase transition temperature. On the other hand, m-PDMA42-PNIPAM37 multiblock copolymer exhibits collapse and intermolecular aggregation, forming associated multimolecular micelles at elevated temperatures. The intriguing aggregation behavior of this novel type of double hydrophilic multiblock copolymers argues well for their potential applications in many fields such as biomaterials and biomedicines.     

Dual-response nanocarrier based on graft copolymers with hydrazone bond linkages for improved drug delivery

Core–shell micelles with biodegradability, thermo- and pH-response were successfully demonstrated by poly(2-oxepane-1,5-dione-co-ɛ-caprolactone) (P(OPD-co-CL)) grafted with hydrophilic segments of amine-terminated poly(N-isopropylacrylamide) (At-PNIPAM). To compare with the graft copolymer, P(OPD-co-CL) block PNIPAM polymer was also prepared. The micelles with core–shell structure were formed with both graft and block copolymers by self-assembly in aqueous solutions, of which PNIPAM shell is thermo-response. Furthermore, P(OPD-co-CL)-g-PNIPAM also showed pH-sensitivity, which was attributed to the acid-cleavable property of the hydrazone bond. The low critical micelle concentrations (CMCs) of graft polymers and block polymers were 6.7 mg/L and 14.3 mg/L, respectively, which indicated the formation of stable micelles. Both drug-free and drug-loaded micelles were in uniformly spherical shape observed by transmission electron microscopy (TEM). The sizes of the drug-free and drug-loaded micelles prepared from graft polymer were 123.5 nm and 146.5 nm, respectively, and the sizes of those prepared from block polymer were 197.5 nm and 211.5 nm, respectively. The lower critical solution temperature (LCST) for the graft polymer was 34.3 °C, while that for the block polymer was 28.1 °C, demonstrating a thermo-response. The graft polymeric micelles exhibited thermo-triggered decelerated release at pH 7.4, and pH-triggered accelerated release at 25 °C in vitro release test, indicating that the graft polymeric micelles could be a promising site-specific drug delivery system for enhancing the bioavailability of the drug in targeted pathological areas.     

Two phase transitions of poly(N-isopropylacrylamide) brushes bound to gold nanoparticles

The thermally induced phase transition of the poly(N-isopropylacrylamide) (PNIPAM) brush covalently bound to the surface of the gold nanoparticles was studied using high-sensitivity microcalorimetry. Two types of PNIPAM monolayer protected clusters (MPCs) of gold nanoparticles were employed, denoted as the cumyl- and the cpa-PNIPAM MPCs, bearing either a phenylpropyl end group or a carboxyl end group on each PNIPAM chain, respectively. The PNIPAM chains of both MPCs exhibit two separate transition endotherms; i.e., the first transition with a sharp and narrow endothermic peak occurs at lower temperature, while the second one with a broader peak occurs at higher temperature. With increase of the MPC concentration, the transition temperature corresponding to the first peak only slightly changes but the second transition temperature strongly shifts to lower temperature. The calorimetric enthalpy change in the first transition is much smaller than that in the second transition. The ratio of the calorimetric enthalpy change to the van't Hoff enthalpy change indicates that in the first transition PNIPAM segments show much higher cooperativity than in the second one. The investigation of pH dependence of two-phase transitions further indicates the PNIPAM brush reveals two separate transitions even with a change in interchain/interparticle association. The observations are tentatively rationalized by assuming that the PNIPAM brush can be subdivided into two zones, the inner zone and the outer zone. In the inner zone, the PNIPAM segments are close to the gold surface, densely packed, less hydrated, and undergo the first transition. In the outer zone, on the other hand, the PNIPAM segments are looser and more hydrated, adopt a restricted random coil conformation, and show a phase transition, which is dependent on both concentration of MPC and the chemical nature of the end groups of the PNIPAM chains. Aggregation of the particles, which may also affect the phase transition, is briefly discussed.     

Switchable photoluminescence of CdTe nanocrystals by temperature-responsive microgels

In the present study, we report a method for preparing a fluorescent thermosensitive hybrid material based on monodisperse, thermosensitive poly( N-isopropyl acrylamide) (PNIPAM) microgels covered with CdTe nanocrystals of 3.2 nm diameter. The CdTe nanocrystals were covalently immobilized on the surface of PNIPAM microgels. The chemical environment around the CdTe nanocrystals was modified by changing the temperature and inducing the microgel volume-phase transition. This change provoked a steep variation in the nanocrystal photoluminescence (PL) intensity in such a way that when the temperature was under the low critical solution temperature (LCST) of the polymer (36 degrees C) the PL of the nanocrystals was strongly quenched, whereas above the LCST the PL intensity was restored.