Designed glucose-responsive microgels with selective shrinking behavior

We report on the synthesis of various glucose-responsive microgels based on N-alkylacrylamide derivatives and phenylboronic acid (PBA) as a glucose sensing moiety. Depending on their chemical composition, the microgels exhibit opposite behaviors in response to glucose concentration increase: they can either swell or shrink, using two different mechanisms for glucose recognition. Both behaviors may be suitable for glucose sensing and insulin delivery. When glucose binds a single boronate receptor, the microgel swells as glucose concentration increases. This mechanism can be used to deliver a drug by diffusion through the network. In other cases, glucose binds specifically to two boronates, which creates additional cross-links within the network and provokes shrinkage. Such systems are promising for the development of sensors with improved selectivity and also as potential "intelligent" valves in microfabricated delivery systems. By a rational choice of the constituting units of the network structure, we show how to favor one or the other type of response to glucose variation. Therefore, glucose-swelling microgels operating under physiological conditions have been obtained by copolymerization with an appropriate choice of alkylacrylamide monomer and boronate derivative. At a pH above the pK(a) of the boronic acid derivative, the same structures shrink in response to glucose concentration. The nature of the cross-linker is a key parameter to enable this dual behavior. In other microgels, an amine group is introduced in the vicinity of the boronic acid, which lowers its pK(a) and favors microgel contraction at physiological pH. This work has allowed us to give some general rules to control the swelling/shrinking behavior of glucose-responsive microgels.     

Grid pattern of nanothick microgel network

A novel grid pattern of two kinds of nanothick microgels was developed by alternate patterning using photolithography. At first, 100-microm-wide nanothick PAAm microgel stripes were grafted on a polystyrene surface by UV irradiation of the photoreactive azidobenzoyl-derivatized polyallylamine-coated surface through a photomask with 100-microm-wide stripes. Then, a second set of 100-microm-wide nanothick PAAc microgel stripes were grafted across the PAAm-grated polystyrene surface by UV irradiation of the photoreactive azidophenyl-derivatized poly(acrylic acid)-coated surface through a photomask placed perpendicularly to the first set of PAAm microgel stripes. The PAAc microgel stripe pattern was formed over the PAAm microgel stripe pattern. The cross angle of the two microgel stripes could be controlled by adjusting the position of the photomask when the second microgel pattern was prepared. Swelling and shrinking of the microgels were investigated by scanning probe microscopy (SPM) in an aqueous solution. SPM observation indicated that the thickness of the gel network was 100 to 500 nm. The regions containing PAAm, PAAc, and the PAAc-PAAm overlapping microgels showed different swelling and shrinking properties when the pH was changed. The PAAm microgel swelled at low pH and shrank at high pH whereas the PAAc microgel swelled at high pH and shrank at low pH. However, the PAAc-PAAm overlapping microgel did not change as significantly as did the two microgels, indicating that the swelling and shrinking of the two gels was partially offset. The pH-induced structural change was repeatedly reversible. The novel grid pattern of nanothick microgels will find applications in various fields such as smart actuators, artificial muscles, sensors, and drug delivery systems as well as in tissue engineering and so forth.     

含铅聚合物微凝胶与硫化氢反应前后在良溶剂中的分子扩散行为

用溶液聚合法制备出轻度交联的含铅微凝胶,用光子相关光谱技术测定其在良溶剂中与H2S反应前、后的扩散行为,由外推法得到在浓度无限稀时的分子扩散系数,给出微凝胶的流体力学半径。结果表明:相同量的含铅微凝胶在不同的初始浓度下与H2S反应,生成含PbS纳米微粒的凝胶；但其体积增大不同,这说明H2S与含铅微凝胶的反应既可以在分子内也可以在分子间进行,分子间的反应使含硫化铅微凝胶扩散系数随浓度的变化曲线的线性范围变小。     

Dual‐Functionalized Crescent Microgels for Selectively Capturing and Killing Cancer Cells

In cancer therapy, the selective targeting of cancer cells while avoiding side effects to normal cells is still full of challenges. Here, we developed dual‐functionalized crescent microgels, which selectively captured and killed lung cancer cells in situ without killing other cells. Crescent microgels with the inner surface of the cavity functionalized with antibody and containing glucose oxidase (GOX) in the gel matrix have been produced in a microfluidic device. These microgels presented high affinity and good selectivity to lung cancer cells and retained them inside the cavities for extended periods of time. Exposing the crescent hydrogels to physiological concentrations of glucose leads to the production of a locally high concentration of H₂O₂ inside the microgels’ cavities, due to the catalytic action by GOX inside the gel matrix, which selectively killed 90 % cancer cells entrapped in the microgel cavities without killing the cells outside. Our strategy to create synergy between different functions by incorporating them in a single microgel presents a novel approach to therapeutic systems, with potentially broad applications in smart materials, bioengineering and biomedical fields.     

Inducing pH responsiveness via ultralow thiol content in polyacrylamide (micro)gels with labile crosslinks

Here we present the synthesis and characterization of pH responsive polyacrylamide microgels, synthesized via free radical polymerization of acrylamide and bis (acryloylcystamine) (BAC). The gels were made with ultralow amounts of thiol functional groups incorporated into the polymer. The resulting gel monoliths were mechanically chopped into microgel particles with size distributions ranging from 80 to 200 mum. The gels exhibit an interesting reversible pH-dependent rheological behavior which led to gelling of the colloidal suspension when the pH was increased, and a low-viscosity suspension was obtained when the pH was taken back to the original value. The viscosity of the colloidal system containing MBA crosslinked microgels remained insensitive to pH. This observation motivated further analysis; viscosity measurements of the highly viscous (gel-like) state of the BAC crosslinked microgel colloidal suspension were carried out to further understand the rheological behavior of the colloidal system. Electrophoretic mobility measurements as function of pH of the BAC and MBA crosslinked colloidal polyacrylamide microgel suspensions were performed. The swelling behavior of the microgels for both colloidal systems was also determined as function of pH using static light scattering. This swelling behavior was used to rationalize the observed rheological behavior. The work presented here demonstrates that free thiol groups present within a polymer gel matrix confer pH responsive behavior to the gel in solution. The viscosity of a BAC crosslinked microgel suspension was also measured under reducing conditions. The viscosity of the microgel suspension reduced with time, due to the breakage of the disulfide bonds in the crosslinkers.     

葡萄糖敏感微凝胶的溶胀动力学研究

通过沉淀聚合法合成了P(NIPAM-co-AA)微凝胶,然后在EDC催化下用3-氨基苯硼酸对微凝胶进行改性,制备了P(NIPAMI-co-AAPBA)微凝胶.红外光谱检测证明改性完全.改性后的微凝胶仍具有很好的温敏性,但由于引入疏水的苯硼酸基团,微凝胶的体积相转变温度大大降低.P(NIPAM-co-AAPBA)微凝胶具...     

Dual-Functionalized Crescent Microgels for Selectively Capturing and Killing Cancer Cells

In cancer therapy, the selective targeting of cancer cells while avoiding side effects to normal cells is still full of challenges. Here, we developed dual-functionalized crescent microgels, which selectively captured and killed lung cancer cells in situ without killing other cells. Crescent microgels with the inner surface of the cavity functionalized with antibody and containing glucose oxidase (GOX) in the gel matrix have been produced in a microfluidic device. These microgels presented high affinity and good selectivity to lung cancer cells and retained them inside the cavities for extended periods of time. Exposing the crescent hydrogels to physiological concentrations of glucose leads to the production of a locally high concentration of H₂O₂ inside the microgels’ cavities, due to the catalytic action by GOX inside the gel matrix, which selectively killed 90 % cancer cells entrapped in the microgel cavities without killing the cells outside. Our strategy to create synergy between different functions by incorporating them in a single microgel presents a novel approach to therapeutic systems, with potentially broad applications in smart materials, bioengineering and biomedical fields.     

Water‐dispersible microgel modified with methacryloyl groups by ionic bonding on the surface and the photopolymer microgel

A novel water‐dispersible reactive microgel, which had a diameter of 40–90 nm, was synthesized for photopolymer materials. The microgels have segments with substituted ammonium groups, to provide water solubility, in their polymer networked structure. It has unsaturated groups connected to the quaternary nitrogens by ionic bonding (I‐type microgel). The I‐type microgel was compared with one that has methacryloyl groups connected with the quaternary nitrogens of the microgel by covalent bonding (C‐type microgel). The I‐type microgels were able to separately control the modified amount of quaternary nitrogen and methacryloyl group. In the presence of 2,4‐diethylthioxantone as a photoinitiator and pentaerthritol triacrylate as a crosslinker, the photopolymer containing the C‐type or I‐type microgels had sensitivity high enough for practical use. Not only the amount of the methacryloyl group of the microgel but the amount of the quaternary nitrogen affected the sensitivity and the rate of polymerization of the water‐dispersible photopolymer containing the I‐type microgels. Copyright © 2000 John Wiley & Sons, Ltd.     

含铅聚合物微凝胶与硫化氢反应前后在良溶剂中的分子扩散行为

用溶液聚合法制备出轻度交联的含铅微凝胶,用光子相关光谱技术测定其在良溶剂中与H₂S反应前、后的扩散行为,由外推法得到在浓度无限稀时的分子扩散系数,给出微凝胶的流体力学半径。结果表明:相同量的含铅微凝胶在不同的初始浓度下与H₂S反应,生成含PbS纳米微粒的凝胶;但其体积增大不同,这说明H₂S与含铅微凝胶的反应既可以在分子内也可以在分子间进行,分子间的反应使含硫化铅微凝胶扩散系数随浓度的变化曲线的线性范围变小。     

Polyurethane acrylate microgel synthesized by emulsion polymerization using unsaturated self-emulsified polymer

Polyurethane (PU) acrylate microgels were obtained by emulsion polymerization of self-emulsified PU acrylate terminated by 2-hydroxyethyl methacrylate without any extra emulsifier and crosslinker. Moreover, the PU acrylate was also used as stabilizer and crosslinker to synthesize poly(methyl methacrylate) (PMMA)–PU composite microgels via emulsion polymerization, which provided a new method to synthesize PU microgels and their composite microgels. The kinetics of microgel synthesis was studied by gel permeation chromatography. The dynamic rheological behaviors indicated that a crosslinked structure was formed. The frequency dependency of the loss tangent and complex viscosities showed strong relationships with the microgel structure. Those microgels with rigid PMMA core showed higher ability to slide than the soft PU acrylate microgel, which had influence on the changing of loss tangent with frequency. All the microgels swollen in tetrahydrofuran exhibited high viscosities and strong shear-thinning behaviors. As a sort of flexible microgel, the PU microgel was able to form a coherent film at room temperature, which was distinct from hard microgels.     

Synthesis and characterization of Poly(N-isopropylacrylamide)/Poly(acrylic acid) semi-IPN nanocomposite microgels

A novel pH- and temperature-sensitive nanocomposite microgel based on linear Poly(acrylic acid) (PAAc) and Poly(N-isopropylacrylamide) (PNIPA) crosslinked by inorganic clay was synthesized by a two-step method. First, PNIPA microgel was prepared via surfactant-free emulsion polymerization by using inorganic clay as a crosslinker, and then AAc monomer was polymerized within the PNIPA microgel. The structure and morphology of the microgel were confirmed by FTIR, WXRD and TEM. The results indicated that the exfoliated clay platelets were dispersed homogeneously in the PNIPA microgels and acted as a multifunctional crosslinker, while the linear PAAc polymer chains incorporated in the PNIPA microgel network to form a semi-interpenetrating polymer network (semi-IPN) structure. The hydrodynamic diameters of the semi-IPN microgels ranged from 360 to 400 nm, which was much smaller than that of the conventional microgel prepared by using N,N′-methylenebis(acrylamide) (MBA) as a chemical crosslinker, the later was about 740 nm. The semi-IPN microgels exhibited good pH- and temperature-sensitivity, which could respond independently to both pH and temperature changes.     

Drying Mechanism of Poly(N-isopropylacrylamide) Microgel Dispersions

The drying mechanism of poly(N-isopropylacrylamide) (pNIPAm) microgel dispersions was investigated. The microgels were synthesized by temperature-programmed aqueous free radical precipitation polymerization using NIPAm, N,N'-methylenebis(acrylamide), and water-soluble initiator. Drying processes of the microgel dispersions were observed with a digital camera and an optical microscope, and the resultant dried structures were observed by scanning electron microscopy. We found that the presence of the microgels changed the behavior of the drying process of water. In particular, the microgels were adsorbed at the air/water interface selectively within a few minutes irrespective of the microgel concentration. The relationship between the drying mechanism and structure of the resultant microgel thin film has been clarified by changing the microgel concentration of the dispersions.     

Unperturbed volume transition of thermosensitive poly-(N-isopropylacrylamide) microgel particles embedded in a hydrogel matrix

The thermoresponsive behavior of poly-(N-isopropylacrylamide) (PNiPAM) microgels embedded in a covalently cross-linked polyacrylamide hydrogel matrix was investigated using ultraviolet-visible (UV-vis) spectroscopy, small-angle neutron scattering (SANS), and confocal laser scanning microscopy. The hydrogel synthesis was performed at two different temperatures, below and above the volume phase transition temperature of PNiPAM, resulting in highly swollen or fully collapsed PNiPAM microgel particles during the incorporation step. UV-vis spectroscopy experiments verify that the incorporation of thermosensitive microgels leads to temperature-sensitive optical properties of the composite materials. SANS measurements at different temperatures show that the thermosensitive swelling behavior of the PNiPAM microgels is fully retained in the composite material. Volume and structure criteria of the embedded microgel particles are compared to those of the free microgels in acrylamide solution. To visualize the temperature responsive behavior of larger PNiPAM particles, confocal fluorescence microscopy images of PNiPAM beads, of 40-microm size, were taken at two different temperatures. The micrographs also demonstrate the retained temperature sensitivity of the embedded microgels.     

Dynamic control of volume phase transitions of poly(N‐isopropylacrylamide) based microgels in water using hydrazide‐aldehyde chemistry

We demonstrate that the volume phase transition temperature (VPTT) of copolymer microgel particles made from N‐isopropylacrylamide (NIPAm) and methacryloyl hydrazide (MH) can be tailored in a reversible manner upon the reaction of the hydrazide functional groups with aldehydes. The microgels were synthesized by precipitation polymerization in water. Due to the water‐soluble nature of the MH monomer, the VPTT at which the microgel particles contract shifts to higher values by increasing the incorporated amounts of methacryloyl hydrazide from 0 to 5.0 mol %. The VPTT of the copolymer microgel dispersions in water can be fine‐tuned upon addition of hydrophobic/hydrophilic aldehydes, which react with the hydrazide moiety to produce the hydrazone analogue. This hydrazone formation is reversible, which allows for flexible, dynamic control of the thermo‐responsive behavior of the microgels. The ability to “switch” the VPTT was demonstrated by exposing hydrophilic streptomycin sulfate salt incubated microgel particles to an excess of a hydrophobic aldehyde, that is benzaldehyde. The temperature at which these microgels contracted in size upon heating was markedly lowered in these aldehyde exchange experiments. Transformation into benzaldehyde hydrazone derivatives led to assembly of the microgel particles into small colloidal clusters at elevated temperatures. This control of supracolloidal cluster formation was also demonstrated with polystyrene particles which had a hydrazide functionalised microgel shell. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1745–1754     

苯硼酸类糖敏感微凝胶制备及其糖敏感性研究

制备了以葡聚糖作为交联剂的氨基苯硼酸类糖敏感微凝胶,用1H-NMR和FT-IR表征了其结构。利用微凝胶的不同条件下的粒径变化,深入研究了该类凝胶对糖浓度的刺激响应行为。结果表明,葡聚糖的引入使微凝胶在生理条件下具有更加优秀的依糖刺激响应行为。     

Zwitterionic microgel based anti(-bio)fouling smart membranes for tunable water filtration and molecular separation

Tunable gating polymeric nanostructured membrane with excellent water permeability and precise molecular separation is highly advantageous for smart nanofiltration application. Polymeric nanostructures such as microgels with functionalizable cross-linkable moieties can be an excellent choice to construct membranes with a thin separation layer, functionality, and tunable transport properties. In the present work, we prepared switchable anti(bio)fouling membranes using zwitterionically functionalized antibacterial thermoresponsive aqueous core-shell microgels with a thin separation layer for controlled filtration and separation applications. The microgels were synthesized using a one-step graft copolymerization of poly(N-isopropylacrylamide) and polyethyleneimine (PEI) followed by zwitterionization of free amine groups of PEI chains with 1,3-propane sultone. Microgel synthesis and zwitterionization were confirmed by spectroscopic and elemntal analysis. The obtained microgels were thoroughly characterized to analyze their thermoresponsive behavior, morphology, charge, and antibacterial properties. After that, characterizations were performed to elucidate the surface properties, water permeation, rejection, and flux recovery of the microgel membranes prepared by suction filtration over a track-etched support. It was observed that zwitterionic membrane provides better hydrophilicity, lower bovine serum albumin (BSA) adsorption, and desirable antimicrobial activity. The pure water permeability was directly related to the microgel layer thickness, applied pressure, and temperature of the feed solution. The novel nanostructured membrane leads to an excellent water permeance with a high gating ratio, high flux recovery rate with low irreversible fouling, better rejection for various dyes, and foulant. Most importantly, the long-term performance of the membrane is appreciable as the microgel layer remains intact and provides excellent separation up to a longer period. Owing to easy preparation and well control over thickness, the zwitterionic microgel membranes constitute unique and interactive membranes for various pressure-driven separation and purification applications.     

Fluorine-containing pH-responsive core/shell microgel particles: preparation,characterization, and their applications in controlled drug release

A kind of novel fluorine-containing pH-responsive core/shell microgels poly(DMAEMA-co-HFMA)-g-PEG were prepared via surfactant-free emulsion polymerization using water as the solvent. The well-defined chemical structure of the copolymers was characterized by FTIR, ¹H-NMR, ¹⁹F-NMR, and elemental analysis. The microgel particles were studied by florescence probe technique, dynamic light scattering, and zeta potential measurement; the microgels displayed a significant pH-responsive behavior. Furthermore, the cytotoxicity assay indicated that the copolymer microgels had low toxicity, and 5-FU-loaded microgels offered a certain killing potency against cancer cells. In addition, the drug loading and in vitro drug release demonstrated that 5-FU was successfully incorporated into polymeric microgels, and the drug-loaded microgels showed a marked pH-dependent drug release behavior. This study suggests that the poly(DMAEMA-co-HFMA)-g-PEG microgels play an important role in the release mechanism stimulated by the change in the pH and have potential applications as a controlled drug release carrier.     

Functionalised Microgels for Acrylic Coatings

Summary: Aqueous acrylic dispersions of hydroxy-functionalised copolymer microgel particles crosslinked with allyl methacrylate were synthesized by emulsion polymerization. The microgels were investigated as reactive polymer fillers in mixtures with a water-borne film-forming dispersion. Properties of coatings cast from mixtures of aqueous dispersion of hard microgel particles and film-forming water-borne dispersion were investigated. The swelling behaviour of microgels in selected solvents (aliphatic ketones) as a function of microgel composition is discussed as well. It was found that the swelling ability of microgels decreased with growing degree of crosslinking. Microgels comprising copolymerised butyl methacrylate swelled less in aliphatic ketones than microgels without this comonomer. This work was focused mainly on the influence of microgels incorporated in the commercial solvent-borne acrylic binders on the properties of coatings. It was shown that the application of microgels that were redispersed in acetone did not affect the surface appearance and transparency of coatings. Moreover, the presence of microgel network precursors accelerated film curing at ambient temperature and improved the final hardness of coatings.     

Temperature-Responsive Poly(N-Isopropylacrylamide-Acrylamide-Phenylboronic Acid) Microgels for Stabilization of Silver Nanoparticles

Poly(N-isopropylacrylamide-acrylamide-phenylboronic acid) [P(NIPAM-AAm-PBA)] microgels of uniform size were prepared by the chemical reaction of 3-aminophenylboronic acid with poly(N-isopropylacrylamide-acrylamide-acrylic acid) [P(NIPAM-AAm-AA)] microgels in aqueous medium in the presence of N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride catalyst via carbodiimide coupling. Silver (Ag) nanoparticles were prepared using seed-mediated growth method and stabilized in P(NIPAM-AAm-PBA)] microgels. Ag nanoparticles and hybrid microgels were characterized by transmission electron microscopy, UV–visible, and dynamic light scattering techniques. The temperature-responsive behavior of hybrid microgels was found to be similar to that of the pure microgels. The value of volume transition temperature of hybrid microgels was found to be slightly higher than that of pure microgels due to shielding effect of Ag nanoparticles present on the surface of microgel particle. The decrease in the size of hybrid microgels as compared to that of pure microgels in swollen state is due to physical cross-linking by Ag nanoparticles inside the network of microgels. The stable hybrid polymer microgel system has a potential to be used for different applications.     

Tuning smart microgel swelling and responsive behavior through strong and weak polyelectrolyte pair assembly

The layer-by-layer (LbL) assembly of polyelectrolyte pairs on temperature and pH-sensitive cross-linked poly(N-isopropylacrylamide)-co-(methacrylic acid), poly(NIPAAm-co-MAA), microgels enabled a fine-tuning of the gel swelling and responsive behavior according to the mobility of the assembled polyelectrolyte (PE) pair and the composition of the outermost layer. Microbeads with well-defined morphology were initially prepared by synthesis in supercritical carbon dioxide. Upon LbL assembly of polyelectrolytes, interactions between the multilayers and the soft porous microgel led to differences in swelling and thermoresponsive behavior. For the weak PE pairs, namely poly(L-lysine)/poly(L-glutamic acid) and poly(allylamine hydrochloride)/poly(acrylic acid), polycation-terminated microgels were less swollen and more thermoresponsive than native microgel, whereas polyanion-terminated microgels were more swollen and not significantly responsive to temperature, in a quasi-reversible process with consecutive PE assembly. For the strong PE pair, poly(diallyldimethylammonium chloride)/poly(sodium styrene sulfonate), the differences among polycation and polyanion-terminated microgels are not sustained after the first PE bilayer due to extensive ionic cross-linking between the polyelectrolytes. The tendencies across the explored systems became less noteworthy in solutions with larger ionic strength due to overall charge shielding of the polyelectrolytes and microgel. ATR FT-IR studies correlated the swelling and responsive behavior after LbL assembly on the microgels with the extent of H-bonding and alternating charge distribution within the gel. Thus, the proposed LbL strategy may be a simple and flexible way to engineer smart microgels in terms of size, surface chemistry, overall charge and permeability.