Tunable Lower Critical Solution Temperature Research Articles

Poly(imidazoled glycidyl methacrylate-co-diethyleneglycol methyl ether methacrylate) – A new copolymer with tunable LCST and UCST behavior in water

A series of poly (imidazoled glycidyl methacrylate-co-diethylene glycol methyl ether methacrylate) copolymers (denoted as P (iGMA-co-MEO2MA)) with different monomer compositions were synthesized and characterized. These copolymers exhibit lower critical solution temperature (LCST) behaviors as the mole ratio of iGMA to MEO2MA in the copolymers range from 0/100 to 1/1, and upper critical solution temperature (UCST) behaviors when this mole ratio ranges from 4/1 to 10/1. The thermoresponsive behaviors of these copolymers were also investigated in water at different pH values. The LCST of the copolymer increased with the iGMA content in the copolymer at pH 6.5, and changed little at pH 7.0, while it decreased with the iGMA content in the copolymer at pH 7.5. Meanwhile, the UCST of the copolymer increased with the iGMA content in the copolymer at pH 6.5 and 7.0. In addition, the thermoresponsive properties of P (iGMA-co-MEO2MA) were influenced by the presence of salt and by the copolymer concentration. This paper offers a facile approach toward thermoresponsive materials with tunable LCST and UCST behaviors.

Poly[oligo(2-ethyl-2-oxazoline)acrylate]-Based Poly(ionic liquid) Random Copolymers with Coexistent and Tunable Lower Critical Solution Temperature- and Upper Critical Solution Temperature-Type Phase Transitions.

The synthesis of a series of dual thermosensitive nonionic-ionic random copolymers with varying compositions by reversible addition-fragmentation chain transfer polymerization is described. These copolymers contain oligo(2-ethyl-2-oxazoline)acrylate (OEtOxA) and either triphenyl-4-vinylbenzylphosphonium chloride ([VBTP][Cl]) or 3- n-butyl-1-vinylimidazolium bromide ([VBuIm][Br]) ionic liquid (IL) units. The copolymers having low content of ionic poly(ionic liquid) (PIL) (P[VBTP][Cl]/P[VBuIm][Br]) segments show only lower critical solution temperature (LCST)-type phase transition with almost linear increase of their cloud points with increasing percentage of ionic PIL segments. Furthermore, LCST-type cloud points ( TcLs) are found very sensitive and tunable with respect to the nature and concentration of halide ions (X- = Cl-, Br-, and I-) and copolymer compositions. However, copolymers with high content of ionic PIL segments show both LCST-type followed by upper critical solution temperature (UCST)-type phase transitions in the presence of halide ions. Dual LCST- and UCST-type phase behaviors are prominent and repeatable for many heating/cooling cycles. Both types of cloud points are found to be sensitive to copolymer compositions, concentration, and nature and concentration of the halide ions. The phase behaviors of both types of copolymers with a very high ionic content (>90%) are exactly similar to that of P[VBTP][Cl] or P[VBuIm][Br] homopolymers showing only UCST-type phase transition in the presence of halide ions. The inherent biocompatibility of the P(OEtOxA) segment along with the interesting dual thermoresponsiveness makes these copolymers highly suitable candidates for biomedical applications including drug delivery.

A Facile Approach for Doxorubicine Delivery in Cancer Cells by Responsive and Fluorescent Core/Shell Quantum Dots.

Biocompatible thermoresponsive copolymers based on 2-(2-methoxyethoxy) ethyl methacrylate (MEO2MA) and oligo (ethylene glycol) methacrylate (OEGMA) were grown from the surface of ZnO quantum dots (QDs) by surface initiated atom transfer radical polymerization with activators regenerated by electron transfer (SI-ARGET ATRP) in order to design smart and fluorescent core/shell nanosystems to be used toward cancer cells. Tunable lower critical solution temperature (LCST) values were obtained and studied in water and in culture medium. The complete efficiency of the process was demonstrated by the combination of spectroscopic and microscopic studies. The colloidal behavior of the ZnO/copolymer core/shell QDs in water and in physiological media with temperature was assessed. Finally, the cytotoxicity toward human colon cancer HT29 cells of the core/shell QDs was tested. The results showed that the polymer-capped QDs exhibited almost no toxicity at concentrations up to 12.5 μg.mL-1, while when loaded with doxorubicin hydrochloride (DOX), a higher cytotoxicity and a decreased HT29 cancer cell viability in a short time were observed.

Designing catechol‐end functionalized poly(DMAm‐co‐NIPAM) by RAFT with tunable LCSTs

ABSTRACTProviding catechol‐end functionality to controlled structure lower critical solution temperature (LCST) copolymers is attractive, given the versatility of catechol chemistry for tethering to nanostructures. Controlled polymer chain lengths with catechol RAFT end groups are of interest to provide tunable LCST behavior to nanoparticles, although these polymerizations are relatively unexplored. Herein, the reactivity ratios for the RAFT copolymerization of N,N‐dimethylacrylamide (DMAm) and N‐isopropylacrylamide (NIPAM) pairs based on catechol‐end RAFT agents using an in situ NMR technique were first determined. Several catechol‐end poly(DMAm‐co‐NIPAM) samples were then prepared using the RAFT agent to provide copolymer. The reactivity ratios for the DMAm‐NIPAM pair were rDMAm = 1.28–1.31 and rNIPAM = 0.48–0.51. All the poly(DMAm‐co‐NIPAM) samples were found to have Mn values ≤ 26 kDa and Ð < 1.08 with LCST values ranging from 31 to 92°C, while maintaining a short range of glass transition temperature (Tg = 118–137°C). The difference in LCST values for the catechol functionalized poly(DMAm‐co‐NIPAM) based on 0.5 wt% aqueous buffered solutions at pH 5.5 and 8.5 was found to be <3.0°C. These conditions are suitable for subsequent catechol‐induced coordination and nucleophilic addition chemistry for covalent and noncovalent linkages during subsequent post‐modification. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 4062–4070

Thermoresponsive poly(poly(ethylene glycol) methylacrylate)s grafted cellulose nanocrystals through SI-ATRP polymerization

We report a series of thermoresponsive cellulose nanocrystals (CNCs) decorated with poly(poly(ethylene glycol) methylacrylate) copolymers (poly(PEGMA)-g-CNCs) synthesized by surface initiated-atom transfer radical polymerization (SI-ATRP). The chemical structures and surface morphologies were subsequently confirmed by FT-IR, XPS, and AFM measurements. With regard to thermally responsive behavior, poly(PEGMA)-g-CNCs show tunable lower critical solution temperature (LCST) values in the range of 34–66 °C by varying the feeding ratios of comonomers. The reversible morphological transformation from individual nano-rod structures to larger globule aggregates was further verified by AFM during the LCST transition. These functionalized CNCs have potential as smart film filters and biosensors.

Smart Polymers and their Applications: A Review

Smart polymers are materials that respond to small external stimuli. These are also referred as stimuli responsive materials or intelligent materials. Smart polymers that can exhibit stimuli-sensitive properties are becoming important in many commercial applications. These polymers can change shape, strength and pore size based on external factors such as temperature, pH and stress. The stimuli include salt, UV irradiation, temperature, pH, magnetic or electric field, ionic factors etc. Smart polymers are very promising applicants in drug delivery, tissue engineering, cell culture, gene carriers, textile engineering, oil recovery, radioactive wastage and protein purification. The study is focused on the entire features of smart polymers and their most recent and relevant applications. Water soluble polymers with tunable lower critical solution temperature (LCST) are of increasing interest for biological applications such as cell patterning, smart drug release, DNA sequencing etc.

Synergistic Thermoresponsive Optical Properties of a Composite Self-Healing Hydrogel

A fast (30 s) thermoresponse and rapid (30 min) self-healing were achieved by noncovalently incorporating a small fraction of poly(N-isopropylacrylamide) (PNIPAM) nanogels (≤0.18 wt %) into a benzyl methacrylate-co-octadecyl methacrylate-co-methacrylic acid (BOMA-16) polymer matrix. The PNIPAM serves as the thermoresponsive component while the BOMA-16 provides self-healing via hydrophobic associations. The PNIPAM/BOMA-16 composite showed tunable lower critical solution temperature and up to 95% more visible light modulation (ΔT) than the same concentration of PNIPAM by itself. Conversely, the PNIPAM nanogels (≤0.18 wt %) served as reinforcements and increased the storage modulus of the PNIPAM/BOMA-16 hydrogel by up to 2.7 times relative to a BOMA-16 hydrogel. Using different analytical techniques, we show that the synergistic thermoresponsive light modulation is due to a hydrophilic–hydrophobic phase transition and clustering of the PNIPAM nanogels facilitated by the BOMA-16. The synergistic optical effec...

Reversibly Tunable Lower Critical Solution Temperature Behavior Induced by H-Bonded Aromatic Amide Macrocycle and Imidazolium Host-Guest Complexation.

A new supramolecular host-guest motif comprising an H-bonded aromatic amide macrocycle and imidazolium cation based ionic liquids was developed, which allows tunable binding affinity via altering N-substitution or counterions. This host-guest system exhibits lower critical solution temperature behavior that can be precisely controlled by adjusting concentration, competitive guest, and acid/base. The demonstrated separation of two organic dyes with the supramolecular complex holds promising applications in separation science.

Dual Thermoresponsive and pH-Responsive Poly(vinyl alcohol) Derivatives: Synthesis, Phase Transition Study, and Functional Applications

Novel poly(vinyl alcohols) (PVA) functionalized with pendant thermo- and pH-responsive groups were prepared by carbonyldiimidazole (CDI)-mediated couplings of N1,N1-diethylethane-1,2-diamine (DEEDA) with controllable modification degree. Nuclear magnetic response (NMR) and IR have verified the successful modification of PVA. The macro- and microscopic phase transition behavior of the obtained PVA-DEEDA-t (t = 10, 30, 70, and 90 h) was thoroughly characterized using various techniques, including turbidity measurement, NMR, and dynamic light scattering (DLS). PVA-DEEDA-t is demonstrated to possess tunable lower critical solution temperature (LCST) between 58 and 24 °C. LCST is dependent on solution pH and degree of PVA modification (14.1–20.9%). By combining DLS and DOSY characterizations, it can be concluded that both coil-to-globule transition and aggregation occurred to PVA-DEEDA-t during phase transition, while only coil-to-globule transition can be detected for the pristine PVA. 2D NOESY proved that th...

Refined control of thermoresponsive swelling/deswelling and drug release properties of poly(N-isopropylacrylamide) hydrogels using hydrophilic polymer crosslinkers

Thermoresponsive poly(N-isopropylacrylamide) (PNIPAm)-based hydrogels are widely investigated for their ability to alter their physical properties (e.g. dimensions, swelling/deswelling) in response to change in temperature. Despite extensive research efforts, it is still challenging to control various aspects of thermoresponsive physical properties of PNIPAm hydrogels in an efficient and comprehensive manner using conventional small molecular crosslinkers due to their limited solubility and functional groups. Herein, thermoresponsive swelling/deswelling behavior of PNIPAm hydrogels is tuned in a wide range by hydrophilic polymeric crosslinkers with varying chain lengths. The concentration and molecular weight of the poly(ethylene glycol) (PEG) crosslinker are varied to control the swelling/deswelling behavior, drug release, and lower critical solution temperature (LCST) of PNIPAm-PEG hydrogels. Compared with PNIPAm hydrogels crosslinked with a conventional small molecular crosslinker, N,N′-methylenebisacrylamide, greater degree and range of thermoresponsive swelling/deswelling as well as tunable LCST are demonstrated for PNIPAm-PEG hydrogels. In addition, more swelling-controlled PNIPAm-PEG hydrogels displayed more sustained and variable thermoresponsive drug release based on their crosslinking density, by modulating the hydrophobic transition of PNIPAm chains with hydrophilic PEG chains. In sum, various thermoresponsive properties of PNIPAm hydrogels could be controlled by hydrophilic polymeric crosslinkers, and this strategy could be applied to various hydrogel systems to control their physical properties for biomedical applications.

Cellulose nanocrystal-poly(oligo(ethylene glycol) methacrylate) brushes with tunable LCSTs

This paper reports on the synthesis of poly(oligoethylene glycol) methyl ether acrylate (POEGMA) grafted cellulose nanocrystals (CNCs) via surface initiated atom transfer radical polymerization (ATRP). An ATRP initiator (α-Bromoisobutyryl bromide) was covalently bonded to the surface of CNCs, followed by copolymerizing di(ethylene glycol) methyl ether methacrylate (MEO2MA) and oligoethylene glycol methyl ether methacrylate (OEGMA300) monomers from the surface using Cu(I)Br/2,2-dipyridal. Multiple POEGMA-g-CNC systems with varying MEO2MA/OEGMA300 content were synthesized, and they displayed a range of lower critical solution temperatures (LCSTs) in aqueous medium. μDSC endotherms and microstructural analysis indicated the collapse of POEGMA chains, followed by the aggregation of nanoparticles above their LCSTs. Cloud point measurements demonstrated a hysteresis in the heating and cooling of the POEGMA-g-CNC systems. It was found that the LCST of the nanoparticles could be tuned to between 23.8 to 63.8°C by adjusting the OEGMA300 content of the POEGMA brushes.

N-Ester-substituted polyacrylamides with a tunable lower critical solution temperature (LCST): the N-ester-substitute dependent thermoresponse

New thermoresponsive polymers ofN-ester-substituted polyacrylamides were discovered, and theN-ester-substitute exerting a great influence on the solution property was demonstrated.

Synthesis and self-assembly behavior of thermo-responsive star-shaped POSS–(PCL–P(MEO2MA-co-PEGMA))16 inorganic/organic hybrid block copolymers with tunable lower critical solution temperature

Star-shaped copolymers have been synthesized and the LCSTs of thermo-responsive micelles were well controlled by adjusting the content of PEGMA.

Multiresponsive micellar block copolymers from 2-vinylpyridine and dialkylvinylphosphonates with a tunable lower critical solution temperature

Tailor-made, multi-responsive micellar AB and ABB′ block copolymers show a pH-sensitivity and a tunable LCST within an expanded temperature range.

Abstract 376: Capture and release of circulating tumor cells by temperature-sensitive graphene oxide-polymer composite

Abstract Introduction and Objective: Recently, various microfluidics-based circulating tumor cells (CTC) isolation technologies have been developed to isolate, enumerate, and characterize CTCs, but there are few studies reporting CTC release after selective capture. Existing devices face impediments to the easy release of captured cells due to the conjugation of antibodies to permanent structures within the devices. Here we present a tunable microfluidic polymer graphene oxide (GO) Chip based on a temperature-sensitive graphene oxide-polymer composite for selective capture and efficient subsequent release of CTCs. Methods: A blend film of GO sheets and thermo-responsive polymers serves as a platform enabling cell capture and release in our microfluidic devices. The polymers with a tunable lower critical solution temperature (LCST) allow for stimulated release of the captured cells when the device temperature is below the LCST. The GO sheets serve as a carrier for phosophlipid-PEG-amine, which is used for the immobilization of an antibody against the epithelial-cell-adhesion-molecule (EpCAM). To investigate the capture efficiency, MCF-7 cells labeled with cell tracker dye were spiked into 1 mL of whole blood and flowed through the microfluidic device. After thoroughly washing the device with PBS at 25 °C to remove any non-specifically bound cells, we dissolved the thermo-responsive composite with 1 mL of PBS at 5 °C in a cold room and collected released cells from the device outlet. The released cells were cytospun and stained to identify CTCs as cytokeratin positive, DAPI positive, and CD45 negative cells. We also tested peripheral blood samples obtained from patients with metastatic breast cancer in a similar manner. Results: The graphene oxide-polymer based CTC-chip showed a capture efficiency of 95.21% at 95.21% and a release efficiency of 92.45% for MCF-7 breast cancer cells. This new GO Chip was also able to isolate viable CTCs from blood samples of metastatic breast cancer patients for further molecular characterizations. Conclusion: We present a sensitive and tunable microfluidic chip based on a GO-polymer composite to capture, release, identify, and characterize extremely rare CTCs. The CTCs released from the chip are viable, suggesting that this polymer based GO Chip offers great potential for clinical applications due to its high-affinity cell capture and the ability to enable various downstream analyses of captured CTCs. Citation Format: Hyeun Joong Yoon, Apoorv Shanker, Yang Wang, Molly Kozminsky, Shamileh Fouladdel, Monika L. Burness, Ebrahim Azizi, Max S. Wicha, Jinsang Kim, Sunitha Nagrath. Capture and release of circulating tumor cells by temperature-sensitive graphene oxide-polymer composite. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 376. doi:10.1158/1538-7445.AM2015-376

A novel nanocomposite hydrogel with precisely tunable UCST and LCST.

Novel thermosensitive nanocomposite (NC) hydrogels consisting of organic/inorganic networks are prepared via in situ free radical polymerization of 2-(2-methoxyethoxy) ethyl methacrylate (MEO2 MA) and oligo(ethylene glycol) methacrylate (OEGMA) in the presence of inorganic cross-linker clay in aqueous solution. The obtained clay/P(MEO2 MA-co-OEGMA) hydrogels exhibit double volume phase transition temperatures, an upper critical solution temperature (UCST), and a lower critical solution temperature (LCST), which can be controlled between 5 and 85 °C by varying the fraction of OEGMA units and the weight percentage of cross-linker clay. These new types of NC hydrogels with excellent reversible thermosensitivity are promising for temperature-sensitive applications such as smart optical switches.

A discrete amphiphilic organoplatinum(II) metallacycle with tunable lower critical solution temperature behavior.

Oligo(ethylene glycol) (OEG)-decorated supramolecular assemblies are distinguished by their neutral character and macroscopic temperature-sensitive phase transition behavior. OEG functionalization is an emerging strategy to obtain thermoresponsive macrocyclic amphiphiles, although known methods organize the hydrophilic and hydrophobic segments by covalent bonding. Coordination-driven self-assembly offers an alternative route for organizing OEG-functionalized precursors into nanoscopic architectures, resulting in well-defined metallacycle cores surrounded by hydrophilic scaffolds to impart overall amphiphilic character. Here a tri(ethylene glycol)-functionalized thermosensitive amphiphilic metallacycle was prepared with high efficiency by means of the directional-bonding approach. The ensembles thus formed showed good lower critical solution temperature behavior with a highly sensitive phase separation and excellent reversibility. Moreover, the clouding point decreased with increasing metallacycle concentration and addition of K(+).

Synthesis and self-assembly behavior of thermoresponsive poly(oligo(ethylene glycol) methyl ether methacrylate)-POSS with tunable lower critical solution temperature

This article reports on the synthesis of a novel amphiphilic polyhedral oligomeric silsesquioxane (POSS) end-capped poly(2-(2-methoxyethoxy)ethyl methacrylate)-co-oligo(ethylene glycol) methacrylate) (POSS-P(MEO2MA-co-OEGMA)). These thermoresponsive organic–inorganic hybrid polymers exhibit critical phase transition temperature in water, which can be finely tuned by changing the feed ratio of OEGMA and MEO2MA. The lower critical solution temperature (LCST) of POSS-P(MEO2MA-co-OEGMA) increases from 31 to 59 °C with the increasing of OEGMA content. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies show that these polymers can self-assemble into spherical micelles with the thermosensitive block into the corona and the POSS forming the core, and larger aggregates are formed when the temperature values are above their LCSTs. These thermoresponsive polymers POSS-P(MEO2MA-co-OEGMA) with self-assembly behavior and tunable tempetature-responsive property have the potential applications in material science and biotechnology.

A NIPAM–Zwitterion Copolymer: Rheological Interpretation of the Specific Ion Effect on the LCST

The effect of various cations and anions on the ability to shield the electrostatic interaction between charged copolymers containing a non‐ionic moiety (N‐isopropylacrylamide (NIPAM)) is explored. The Hofmeister series, first noted in 1888, ranks the relative influence of ions on the physical behavior of a wide variety of aqueous processes ranging from colloidal assembly to protein folding. The viscoelastic behavior of a poly(NIPAM‐co‐Zw10%) solution as a function of ionic strength in the presence of different ions is rheologically investigated. The obtained copolymer exhibits a thermoresponsive behavior, with tunable lower critical solution temperature (LCST) ranging from 28 to 33 °C. The viscosity change specifically demonstrates the effectiveness of the low‐molecular‐weight ions in weakening the inter‐/intramolecular electrostatic crosslinks among the sulfobetaine chain and in enhancing the hydration of the macromolecule. The effectiveness of the anions follows the Hofmeister series while that of the cations follows the reversed Hofmeister series, as demonstrated by Collins' concept of “matching water affinity,” due to presence of a sulfobetaine group in the chains. image

Well-Defined Thermoresponsive Copolymers with Tunable LCST and UCST in Water

permeation chromatography (GPC) and 1 H NMR spectroscopy. The transmission spectra of the 1.0 wt % aqueous solutions of the resulting polymers at 650 nm were measured as a function of temperature. Results showed that the lower critical solution temperature (LCST) and the upper critical solution temperature (UCST) could be easily controlled by the different composition of dimethylamino and zwitterion groups. The effect of partial quaternization on thermoresponsive properties was also studied by dynamic light scattering (DLS) with the same aqueous concentration (1.0 wt %) as employed for turbidimetry studies. The LCST and UCST values measured by DLS correlated well with those determined by turbidimetry.