Fabrication of Micropatterned Gold Nanoparticle Arrays as a Template for Surface‐Initiated Polymerization of Stimuli‐Responsive Polymers

Summary: This paper demonstrates a new, reliable, and simple method for fabricating micropatterned nanoparticle arrays that can serve as templates for the surface‐initiated polymerization of polymer brushes. As a proof of concept, we micropatterned gold nanoparticles (Au‐NPs, ≈10 nm) onto glass, silicon, polystyrene, and gold surfaces by a simple three‐step process: (1) microcontact printing of soluble polymer, (2) incubation with a solution of Au‐NPs, and (3) lift‐off of the template in a mixture of ethanol and deionized water. 40 µm wide features were successfully fabricated without any significant defects or nonspecific adsorption on the background. To demonstrate the utility of these Au‐NP templates, we subsequently polymerized N‐isopropylacrylamide by surface‐initiated polymerization, using a surface‐bound initiator.

Synthesis of PNIPAAm brushes from micropatterned Au‐NP.     

Recent development of temperature‐responsive cell culture surface using poly(N‐isopropylacrylamide)

Poly(N‐isopropylacrylamide) (PIPAAm), which is a well‐known temperature‐responsive polymer, is modified on substrates by various methods. At 37 °C, PIPAAm modified surface is hydrophobic and allows cells to adhere to and proliferate on the surface. By reducing temperature below the lower critical solution temperature of PIPAAm, the surface turns to hydrophilic and allows cells to detach themselves from the surface spontaneously. With this technology, cell sheet engineering is established several years ago. This review focuses on the preparations and characteristics of PIPAAm‐modified surfaces, and discusses the effect of surface properties on cell adhesion and deadhesion. In addition, the recent improvement of PIPAAm‐modified surfaces for cell culture and the clinical applications of cell sheets harvested from the surfaces are also mentioned. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014 , 52, 917–926     

Investigation of swelling,drug release and diffusion behaviors of poly(N‐isopropylacrylamide)/poly (N‐vinylpyrrolidone) full‐IPN hydrogels

The synthesis of sequential full interpenetrating polymer networks (IPNs) based on poly (N‐isopropylacrylamide) (PNIPAAm) and negatively charged poly(N‐vinyl‐2‐pyrrolidone) (PNVP) was described and their swelling, drug release, and diffusion studies were investigated. PNIPAAm was used as a host network. According to swelling experiments, IPNs gave relatively lower swelling ratios compared to PNIPAAm hydrogel due to the higher cross‐linking density. Lidocaine (LD) was used as a model drug for the investigation of drug release behavior of IPNs. LD uptake of the IPNs were found to increase from 24 to 166 (mg LD / g dry gel) with increasing amount of PNIPAAm and AMPS contents in the IPN structure. It was observed that the specific interaction between drug and AMPS co‐monomer influenced the drug release profile. In the diffusion transport mechanism study in water, the results indicated that the swelling exponents n for all IPNs are in the range from 0.50 to 0.72. This implies that the swelling transport mechanism was transferred from Fickian to non‐Fickian transport, with increasing AMPS content and NIPAAm character in the IPN structure. In addition, diffusion of LD within the IPNs showed similar trend. The incorporation of AMPS leads to an increase in electrostatic interaction between charge sites on carboxylate ions and cationic LD molecules. Therefore, the highest diffusion coefficient (D) of drug was found for IPN2 sample. Copyright © 2007 John Wiley & Sons, Ltd.     

Microfluidic chip with thermoresponsive boronate affinity for the capture–release of cis‐diol biomolecules

The polydimethylsiloxane microfluidic chip grafted with poly(N‐isopropylacrylamide‐3‐acrylamidephenylboronic acid) (P(NIPAAm‐co‐AAPBA)) was fabricated by UV‐induced grafting polymerization for the capture–release of cis‐diol‐containing biomolecules by temperature‐modulated changes instead of changing the pH value of the mobile phase. Based on the optimal time for benzophenone soaking and UV irradiation of grafting polymerization, P(NIPAAm‐co‐AAPBA) was successfully grafted on the polydimethylsiloxane substrates, which were characterized by scanning electron microscopy, water contact angle measurements, and Fourier transform infrared spectroscopy. The P(NIPAAm‐co‐AAPBA)‐grafted polydimethylsiloxane microfluidic chip can be successfully used for the capture and release of cis‐diol‐containing adenosine by adjusting the temperature from 4 to 55°C, and the result was validated by Triple Quad liquid chromatography with mass spectrometry. With further development, the fabricated polydimethylsiloxane microfluidic chips might be chosen as a potential tool for the capture and release of cis‐diol‐containing macromolecules, such as horseradish peroxidase and glycoprotein.     

Formation of a Polypseudorotaxane via Self‐Assembly of γ‐Cyclodextrin with Poly(N‐isopropylacrylamide)

A polypseudorotaxane (PPR) comprising γ‐cyclodextrin (γ‐CD) as host molecules and poly(N‐isopropylacrylamide) (PNIPAM) as a guest polymer is prepared via self‐assembly in aqueous solution. Due to the bulky pendant isopropylamide group, PNIPAM exhibits size‐selectivity toward self‐assembly with α‐, β‐, and γ‐CDs. It can fit into the cavity of γ‐CD to give rise to a PPR, but cannot pass through α‐CD and β‐CD under the same conditions. The ratio of the number of γ‐CD molecules to entrapped NIPAM repeat units is kept at 1:2.2 or 1:2.4, determined by ¹H NMR spectroscopy and TGA analysis, respectively, indicating that there are more than 2 but less than 3 NIPAM repeat units included by one γ‐CD molecule. This finding opens new avenues to PPR‐based supramolecular polymers to be used as solid, stimuli‐responsive materials.     

Novel temperature‐ and pH‐responsive graft copolymers composed of poly(L‐glutamic acid) and poly(N‐isopropylacrylamide)

A series of novel temperature‐ and pH‐responsive graft copolymers, poly(L ‐glutamic acid)‐g‐poly(N‐isopropylacrylamide), were synthesized by coupling amino‐semitelechelic poly(N‐isopropylacrylamide) with N‐hydroxysuccinimide‐activated poly(L ‐glutamic acid). The graft copolymers and their precursors were characterized, by ESI‐FTICR Mass Spectrum, intrinsic viscosity measurements and proton nuclear magnetic resonance (¹H NMR). The phase‐transition and aggregation behaviors of the graft copolymers in aqueous solutions were investigated by the turbidity measurements and dynamic laser scattering. The solution behavior of the copolymers showed dependence on both temperature and pH. The cloud point (CP) of the copolymer solution at pH 5.0–7.4 was slightly higher than that of the solution of the PNIPAM homopolymer because of the hydrophilic nature of the poly(glutamic acid) (PGA) backbone. The CP markedly decreased when the pH was lowered from 5 to 4.2, caused by the decrease in hydrophilicity of the PGA backbone. At a temperature above the lower critical solution temperature of the PNIPAM chain, the copolymers formed amphiphilic core‐shell aggregates at pH 4.5–7.4 and the particle size was reduced with decreasing pH. In contrast, larger hydrophobic aggregates were formed at pH 4.2. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4140–4150, 2008     

Synthesis and thermoresponsive property of end‐functionalized poly(N‐isopropylacrylamide) with pyrenyl group

N–Isopropylacrylamide (NIPAM) was polymerized using 1‐pyrenyl 2‐chloropropionate (PyCP) as the initiator and CuCl/tris[2‐(dimethylamino)ethyl]amine (Me₆TREN) as the catalyst system. The polymerizations were performed using the feed ratio of [NIPAM]₀/[PyCP]₀/[CuCl]₀/[Me₆TREN]₀ = 50/1/1/1 in DMF/water of 13/2 at 20 °C to afford an end‐functionalized poly(N‐isopropylacrylamide) with the pyrenyl group (Py–PNIPAM). The characterization of the Py–PNIPAM using matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry provided the number–average molecular weight (M_n,MS). The lower critical solution temperature (LCST) for the liquid–solid phase transition was 21.7, 24.8, 26.5, and 29.3 °C for the Py–PNIPAMs with the M_n,MS's of 3000, 3400, 4200, and 5000, respectively; hence, the LCST was dramatically lowered with the decreasing M_n,MS. The aqueous Py–PNIPAM solution below the LCST was characterized using a static laser light scattering (SLS) measurement to determine its molar mass, M_w,SLS. The aqueous solutions of the Py–PNIPAMs with the M_n,MS's of 3000, 3400, 4200, and 5000 showed the M_w,SLS of 586,000, 386,000, 223,000, and 170,000, respectively. Thus, lowering the LCST for Py–PNIPAM should be attributable to the formation of the PNIPAM aggregates. The LCST of 21.7 °C for Py–PNIPAM with the M_n,MS of 3000 was effectively raised by adding β‐cyclodextrin (β‐CD) and reached the constant value of ～26 °C above the molar ratio of [β‐CD]/[Py–PNIPAM] = 2/1, suggesting that β‐CD formed an inclusion complex with pyrene in the chain‐end to disturb the formation of PNIPAM aggregates, thus raising the LCST. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1117–1124, 2006     

Switchable phase transition behavior of thermoresponsive substrates for cell sheet engineering

Recently, there are significant interests in the development of biomaterials with nonlinear response to an external stimulus. Thermoresponsive polymers as a well-known class of stimuli-responsive materials represent reversible hydrophilicity/hydrophobicity characteristics around a critical temperature. This switchable behavior applies for nondestructive cellular detachment from cultivation substrates. In this study, poly (N-isopropylacrylamide) (PNIPAAm)-grafted dishes were made up to harvest retinal pigmented epithelial (RPE) and periodontal ligament cell (PDLC) sheets. Wettability assessments verified that all functionalized surfaces were inverted from hydrophilic to hydrophobic state when the temperature rises from lower critical solution temperature (LCST) at 37 °C. Other physicochemical characteristics such as chemical composition, grafting thickness, and surface topography were investigated through attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and atomic force microscopy (AFM). ATR-FTIR results showed typical peaks of amide group corresponding to successful PNIPAAm polymerization. AFM microscopy results also proved creating a rough PNIPAAm layer with thickness of 29.2 nm after grafting process in the mixture of methanol and water. Cell culture experiments showed an irreversible cellular attachment/detachment from modified surfaces upon temperature changes. These results introduced thermoresponsive TCPS to noninvasively harvest RPE and PDLCs sheets especially for application in scaffold-free tissue engineering decorations. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018 , 56, 1567–1576     

SET‐LRP of N,N‐dimethylacrylamide and of N‐isopropylacrylamide at 25 °C in protic and in dipolar aprotic solvents

The single‐electron transfer living radical polymerization (SET‐LRP) of water‐soluble monomers, N,N‐dimethylacrylamide (DMA) and N‐isopropylacrylamide (NIPAM), initiated with 2‐methylchloropropionate (MCP) in dipolar aprotic and protic solvents is reported. The radical polymerization of acrylamides is characterized by higher rate constants of propagation and bimolecular termination than acrylates. Therefore, the addition of CuCl₂ is required to mediate deactivation in the early stages of the reaction. Through the use of Cu(0)‐wire/Me₆‐TREN catalysis, conditions were optimized to minimize the amount of externally added CuCl₂ required to maintain a linear evolution of molecular weight and narrow molecular weight distribution. By using less CuCl₂ additive, the amount of soluble copper species that must ultimately be removed from the reaction mixture is reduced. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1752–1763, 2010     

Molecular Dynamics Investigation of the Thermo‐Responsive Polymer Poly(N‐isopropylacrylamide)

Using molecular dynamics simulations with an OPLS force field, the lower critical solution temperature (LCST) of single‐ and multiple‐chain PNIPAM solutions in water is investigated. The sample containing ten polymer chains shows a sudden drop in size and volume at 305 K. Such an effect is absent in the single‐chain system. Large fluctuations of the physical properties of a short single‐chain prevent any clear detection of the LCST for the chosen model system, at least on the time scale of 200 ns. The results provide evidence that a critical number of PNIPAM monomer units must be present in the simulated system before MD simulations are capable to detect conformational changes unambiguously.

     

Synthesis of magnetic,reactive, and thermoresponsive Fe3O4 nanoparticles via surface‐initiated RAFT copolymerization of N‐isopropylacrylamide and acrolein

A reversible addition‐fragmentation chain transfer (RAFT) agent was directly anchored onto Fe₃O₄ nanoparticles in a simple procedure using a ligand exchange reaction of S‐1‐dodecyl‐S′‐(α,α′‐dimethyl‐α″‐acetic acid)trithiocarbonate with oleic acid initially present on the surface of pristine Fe₃O₄ nanoparticles. The RAFT agent‐functionalized Fe₃O₄ nanoparticles were then used for the surface‐initiated RAFT copolymerization of N‐isopropylacrylamide and acrolein to fabricate structurally well‐defined hybrid nanoparticles with reactive and thermoresponsive poly(N‐isopropylacrylamide‐co‐acrolein) shell and magnetic Fe₃O₄ core. Evidence of a well‐controlled surface‐initiated RAFT copolymerization was gained from a linear increase of number‐average molecular weight with overall monomer conversions and relatively narrow molecular weight distributions of the copolymers grown from the nanoparticles. The resulting novel magnetic, reactive, and thermoresponsive core‐shell nanoparticles exhibited temperature‐trigged magnetic separation behavior and high ability to immobilize model protein BSA. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 542–550, 2010     

Hydration‐mediated effects of saccharide stereochemistry on poly(N‐isopropylacrylamide) gel swelling

To shed new light on the mechanisms of saccharide stereochemistry effect on macromolecules in aqueous solutions, we studied the effect of three monosaccharide stereoisomers, glucose, galactose, and mannose, on the swelling of Poly(N‐isopropylacrylamide) (PNIPA) hydrogels. We equilibrated PNIPA hydrogels in sugar solutions of different concentrations at 25 °C, and determined gel volume and mass swelling ratios, and sugar concentration imbalance. The volume‐phase‐transition occurred at molal concentrations of 0.587 ± 0.004 (galactose), 0.724 ± 0.003 (glucose), and 0.846 ± 0.004 (mannose). The same order of sugars emerged for the gel‐swelling and the magnitude of the sugar concentration‐imbalance, which correlated with sugar isentropic molar compressibility and hydration number. The more hydrated the sugar, the worse a cosolvent it is for the polymer, hence the larger the deswelling and the more negative the sugar concentration imbalance. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011     

Preparation and properties of poly(N‐isopropylacrylamide)/poly(N‐isopropylacrylamide) interpenetrating polymer networks for drug delivery

A novel poly(N‐isopropylacrylamide) (PNIPA)/PNIPA interpenetrating polymer network (IPN) was synthesized and characterized. In comparison with conventional PNIPA hydrogels, the shrinking rate of the IPN hydrogel increased when gels, swollen at 20 °C, were immersed in 50 °C water. The phase‐transition temperature of the IPN gel remained unchangeable because of the same chemical constituent in the PNIPA gel. The reswelling kinetics were slower than those of the PNIPA hydrogel because of the higher crosslinking density of the IPN hydrogel. The IPN hydrogel had better mechanical strength because of its higher crosslinking density and polymer volume fraction. The release behavior of 5‐fluorouracil (5‐Fu) from the IPN hydrogel showed that, at a lower temperature, the release of 5‐Fu was controlled by the diffusion of water molecules in the gel network. At a higher temperature, 5‐Fu inside the gel could not diffuse into the medium after a burst release caused by the release of the drug on the surface of the gel. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1249–1254, 2004     

Photoluminescent Toroids Formed by Temperature‐Driven Self‐Assembly of Rhodamine B End‐Capped Poly(N‐isopropylacrylamide)

In this paper, self‐assembled polymeric toroids formed by a temperature‐driven process are reported. Rhodamine B (RhB) end‐capped poly(N‐isopropylacrylamide) (PNIPAAm) demonstrating a lower critical solution temperature (LCST) is prepared. In a two‐phase system, the polymer in the aqueous phase could move to the chloroform phase on raising the temperature above its LCST. This temperature‐driven process results in the formation of polymeric toroids in the chloroform phase, and the strategy affords a new pathway to toroidal self‐assembly of polymers. Moreover, the photoluminescent behavior of the RhB end‐capped PNIPAAm species formed by the process is also studied and discussed.

     

Compressive Elastic Moduli of Poly(N‐Isopropylacrylamide) Hydrogels Crosslinked with Poly(Dimethyl Siloxane)

Hydrophobically modified and thermally reversible neutral and ionic copolymer hydrogels were prepared from N‐isopropylacrylamide (NIPAAm), vinyl terminated poly (dimethylsiloxane) (VTPDMS) and itaconic acid (IA) by free radical solution polymerization, and their properties such as swelling ratio and compression modulus were studied at the 25°C. The incorporation of VTPDMS as a hydrophobic macrocrosslinker into the structures of neutral NIPAAm hydrogels increased their mechanical strength around 10 times than those of the ones crosslinked with conventional tetra functional monomer, i.e., N,N′‐methylene bisacrylamide (BIS). Compression modulus decreased with an increase in IA content for ionic samples and increased with increasing molecular weight and content of VTPDMS for neutral samples. It was assumed that in the first case, electrostatic repulsive forces resulting from the ionized carboxyl groups of IA were responsible for decreasing mechanical strength, while in the second case, hydrophobic interactions between dimethylsiloxane units of VTPDMS chains enhanced the compression moduli. According to the results presented in this work, it can be said that the right balance of hydrophobic and hydrophilic constituents and adjustment of the number of ionized groups, as well as crosslinking degree, change the structure and physical properties of NIPPAAm hydrogels.     

Fabrication of Silver Nanoparticles in Hydrogel Networks

Summary: This paper describes a simple and facile approach to fabricate well dispersed silver nanoparticles (AgNPs) in poly[N‐isopropylacrylamide‐co‐(sodium acrylate)] hydrogels. The silver nanoparticles formed are spherical in shape with a narrow size distribution in the hydrogel networks in which the nanoparticles are stabilized by the polymer network. Uniformly dispersed silver nanoparticles were obtained with poly[N‐isopropylacrylamide‐co‐[sodium acrylate)] hydrogels, whereas a poly(N‐isopropylacrylamide)/poly(sodium acrylate) IPN gel showed aggregated nanoparticles. It is demonstrated that the hydrogel network structure determines the size and shape of the nanoparticles. These particles are more stable in the gel networks compared to other reduction methods. The hydrogel/silver nanohybrids were well characterized by XRD, UV‐vis spectrometry, scanning electron microscopy and transmission electron microscopy.

Schematic representation of the preparation of Ag nanoparticles in hydrogel networks.     

Micro ATR‐FTIR study of the hydration state of poly(N‐tert‐butylacrylamide‐co‐acrylamide) copolymers during phase transition in aqueous media and in the mixture of water–methanol

Coil‐globule transition of poly(N‐tert‐butylacrylamide‐co‐acrylamide) P(NTBAM‐co‐AM) copolymers is investigated in the aqueous solution and in the mixture of water–methanol by micro ATR‐FTIR spectroscopy technique. In this study the microstructure and its changes in the hydration states of the distinct groups of these copolymers are investigated by micro ATR/FTIR technique. The results showed that by heating the solution above the LCST hydrogen bonding between C?O and water was decreased but the hydrogen bonding between polymeric chains increased, which prove the aggregation of polymer chain during phase separation. The chemical shifts of IR bands are also studied in the mixture of water–methanol. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 356–363, 2010     

Encapsulation of Bovine Serum Albumin in Temperature‐Programmed “Shell‐in‐Shell” Structures

A novel approach to load a hydrophilic bovine serum albumin into drug carriers was proposed in terms of temperature‐programmed “shell‐in‐shell” structures, which were fabricated with poly(N‐isopropylacrylamide), poly(lactide), poly(ethylene glycol), and Au nanoparticles. Spherically well‐defined “shell‐in‐shell” structures were constructed by a modified‐double‐emulsion method (MDEM). The lower critical solubility temperature of the structures was manipulated to 36.4 °C which was confirmed by UV/Vis spectroscopy and DSC (Differential Scanning Calorimetry).

TEM image of the Au@PLLA‐PEG@PNIPAAm‐PDLA structure.     

Robust Poly(allylamine)‐graft‐poly(N‐isopropylacrylamide) Particles Prepared by Physical Crosslinking with Poly(styrene sulfonate)

Summary: Robust thermosensitive PAH‐g‐PNIPAAm/PSS particles were prepared by addition of a poly(allylamine)‐graft‐poly(N‐isopropylacrylamide) particle suspension into poly(styrene sulfonate) solution above the LCST of PAH‐g‐PNIPAAm. Scanning force microscopy revealed stable and well‐separated particles in water at room temperature. The zeta‐potential showed a negative surface charge of the particles. Their thermosensitive behavior was demonstrated by dynamic light scattering. The release of rhodamine 6G loaded particles could respond to the incubation temperature.

Fabrication of thermosensitive and robust particle by suspension of in situ formed PAH‐g‐PNIPAAm particle above the LCST in PSS solution.     

Preparation and separation function of N‐isopropylacrylamide copolymer hydrogels

In this paper, N‐isopropylacrylamide (NIPA) was synthesized by acrylonitrile and isopropanol. Poly(N‐isopropylacrylamide) (PNIPA) was prepared by a chemical method. The dependence of its swelling behavior on temperature was studied. Results showed that PNIPA hydrogel was a temperature‐sensitive gel. Its LCST (lower critical solution temperature) was about 32 °C, and its swelling ratio (at 20 °C) was about 17–18. Sodium acrylate (SA) and sodium methylacrylate (SMA) were copolymerized with NIPA respectively. Equilibrium swelling ratios of the copolymer hydrogels at lower temperature were two to three times that of PNIPA. The LCST of the copolymer hydrogels could be controlled between 32 and 45 °C by adjusting the content of SA or SMA. Kinetics of P(NIPA‐co‐SA) hydrogels, whether swelling or shrinking processes, were in good agreement with apparent second order kinetic equations. Several experiments were designed to separate aqueous bovine serum albumin solution using the hydrogels prepared above. The separation efficiency was about 80%. Copyright © 2000 John Wiley & Sons, Ltd.