magnetic-thermal-sensitive-poly-n-isopropylacrylamide-based-microgels

Magnetic and Thermal-sensitive Poly(<em>N</em>-isopropylacrylamide)-based Microgels for Magnetically Triggered Controlled Release

Magnetically and thermally sensitive poly(N-isopropylacrylamide) (PNIPAAm)/Fe3O4-NH2 microgels with the encapsulated anti-cancer drug curcumin (Cur) were ...

National Taiwan University

A core-shell copolymer latex with thermal-responsive properties was prepared and its potential application as a vehicle for drug targeting was investigated in this work, where the crosslinked copolymer of N-isopropylacrylamide (NIPAAm) and chitosan was prepared as the core and the copolymer of methacrylic acid (MAA) and methyl methacrylate (MMA) was prepared as the shell. By using soapless dispersion polymerization, the poly(NIPAAm-chitosan) crosslinked copolymer latex was synthesized first. Then the monomers of MAA and MMA were added to continue the reaction to obtain the core-shell copolymer latex. The weight ratio of MAA/MMA and the concentration of shell monomers (MAA and MMA) in the feed of the reaction mixture had been changed to investigate their effects on the particle size, reaction rate, zeta-potential, specific surface area, and surface functional groups of the latex particles. The swelling and thermoresponsive behavior of the film made from these core-shell latices were also studied under different pH values of buffer solution. The model drug (caffeine) could be merged inside the copolymer particles and protected from releasing through the transport process effectively. And the thermoresponsive property of these copolymer particles significantly enhances the ligand (protein) conjugation that shows the potential of the latex being applied on the targeting drug carrier.

Preparation of thermoresponsive core-shell copolymer latex with potential use in drug targeting.

Ferrofluids, which are stable dispersions of magnetic particles, behave as liquids that have strong magnetic properties. Nanoparticles of magnetite with a mean diameter of 10-15 nm, which are in the range of superparamagnetism, are usually prepared by the traditional method of co-precipitation from ferrous and ferric electrolyte solution. When diluted, the ferrofluid dispersions are not stable if anionic or cationic surfactants are used as the stabilizer. This work presents an efficient way to prepare a stable aqueous nanomagnetite dispersion. A stable ferrofluid containing Fe3O4 nanoparticles was synthesized via co-precipitation in the presence of poly(acrylic acid) oligomer. The mechanism, microstructure, and properties of the ferrofluid were investigated. The results indicate that the PAA oligomers promoted the nucleation and inhibited the growth of the magnetic iron oxide, and the average diameter of each individual Fe3O4 particle was smaller than 10 nm. In addition, the PAA oligomers provided both electrostatic and steric repulsion against particle aggregation, and the stability of dispersions could be controlled by adjusting the pH value of solution. A small amount of Fe2O3 was found in the nanoparticles but the superparamagnetic behavior of the nanoparticles was not affected.

Preparation and properties of poly(acrylic acid) oligomer stabilized superparamagnetic ferrofluid.

PHAs (poly-3-hydroxyalkanoates) obtained by Pseudomonas oleovorans grown with mixed carbon sources were investigated. Mixed carbon sources were sodium octanoate/undecylenic acid and sodium octanoate/5-phenylvaleric acid. Effect of carbon source in pre-culture on PHAs structure was investigated. Main fermentation was conducted with mixture of sodium octanoate/undecylenic acid, and PHA contained both saturated and unsaturated units. When more undecylenic acid was used in the medium, the ratio of unsaturated unit increased and the T(g) of the products also changed. The PHA grown with mixture of sodium octanoate and undecylenic acid was a random copolymer, which was determined by DSC analysis. Using mixed carbon sources of sodium octanoate and 5-phenylvaleric acid, highest dry cell weight and PHA concentration were obtained when 0.02g or 0.04g of 5-phenylvaleric acid were added in 50mL medium. Cultured with sodium octanoate and 5-phenylvaleric acid, PHA containing HO (3-hydroxyoctanoate) unit and HPV (3-hydroxy-5-phenylvalerate) unit was produced. T(g) of the products fell between those of pure PHO and pure PHPV. By means of DSC analysis and fractionation method, the PHA obtained was regarded as a random copolymer.

Structure and polymer form of poly-3-hydroxyalkanoates produced by Pseudomonas oleovorans grown with mixture of sodium octanoate/undecylenic acid and sodium octanoate/5-phenylvaleric acid.

Nano-sized TiO(2) or SiO(2)/TiO(2) particles were prepared by hydrolysis and condensation reactions in aqueous media, followed by mixing with poly(AA-co-MMA) latex to form different composites, then blending with poly(ethylene terephthalate), PET. The TGA results of composites indicated that negative charged latexes had greater interaction with TiO(2)/ or SiO(2)/TiO(2) particles through strong electrostatic forces, while cationic latexes incorporated with TiO(2) or SiO(2)/TiO(2) particles by pH induced coagulation, carbonyl group chelation and hydrogen bonding. The soapless latex polymer particles showed lower ability of adsorption to TiO(2) particles due to the decrease of total surface area of these larger particles. If SiO(2)/TiO(2) particles were used instead of TiO(2) particles, unexpected high adsorption result was observed. Morphology results observed by SEM showed that PET blended with positive charged composites was more homogeneous than PET blended with negative charged composites. DSC results also indicated that the T(g) of PET was increased, melting temperatures (T(m) or T(m)(')) were increased, and the temperature range of crystallization was narrowed after blending with the composites. The presence of composites affected the mobility and packing of PET molecular chains therefore changing the thermal properties of PET.

Synthesis of nano-sized TiO(2)/poly(AA-co-MMA) composites by heterocoagulation and blending with PET.

In this work, poly(acrylic acid-co-sodium acrylate) P(AA-SA) latex particles were prepared by inverse miniemulsion polymerization and used as a pH buffering agent for application. The polymerization was quickly initiated by a redox initiator (ammonium persulfate/sodium metabisulfite) at 0-5 degrees C. Thus the possibility of monomer dissolving in a solvent was reduced, which enhanced the degree of droplet nucleation. The effects of costabilizer and the ratio of SA/(AA+SA) in functional latex particles on the nucleation mechanism and emulsion stability were investigated. The apparent pK(a) values of the synthesized P(AA-SA) latex particles were determined by titration experiments. Their properties on pH buffering were also studied, including the pH temporal response and pH buffering ability. The results showed that sodium hydroxide, which was introduced as the costabilizer to enhance the osmotic pressure and to increase the deprotonation of acrylic acid, was effective in guaranteeing droplet nucleation predominantly. Meanwhile, the surfactant concentration was controlled to be less than its critical micelle concentration (CMC) value to avoid micellar nucleation. Furthermore, the P(AA-SA) latex particles thus synthesized were found to be an excellent material for pH buffering. The pH temporal response was very rapid and related to the crosslinking degree of the latex particles. The terminal range of pH buffering for latex particles was controllable by the ratio of SA/(AA+SA).

P(AA-SA) latex particle synthesis via inverse miniemulsion polymerization-nucleation mechanism and its application in pH buffering.

Flexible polymer films with high electrical conductivity were prepared through a simple coating of well-dispersed silver nanoparticle (AgNP) and multiwalled carbon nanotube (CNT) solution. The hybrid film with surface resistance as low as 1 × 10(-2) Ω/sq was prepared by controlling the annealing temperature in air and by using a suitable composition of silver nitrate/CNT/poly(oxyethylene)-oligo(imide) (POE-imide) in the ratio 20:1:20 by weight. During the heating, color of the film surface changed from black to golden to milky white, indicating the accumulation of AgNPs through surface migration and melting into CNT-connected networks. Thermogravimetric measurements showed that the transition temperature of 170 °C was responsible for the POE-imide degeneration and the subsequent Ag melting with a decrease in the surface resistance from 2.1 × 10(5) to 2.0 × 10(-1) Ω/sq, which was able to illuminate light-emitting diode lamps because of the formation of a continuous Ag network.

Controlling formation of silver/carbon nanotube networks for highly conductive film surface.

This study reports on the time-resolved polymer propagation of thermal-sensitive latex nanoparticles containing Fe3O4 cores. The latex shells are made with poly(N-isopropylacrylamide-co-acrylic acid) (Fe3O4/P(NIPAAm-co-AAc)) at different reaction times. The Fe3O4 particles are first modified using AAc monomers. The AAc-modified Fe3O4 cores are then copolymerized with NIPAAm to form the latex shell. The Fe3O4 cores in the latex nanoparticles are confirmed using X-ray photoelectron spectroscopy (XPS), X-ray diffraction spectroscopy (XRD), and thermo gravimetric analyzer (TGA). As the reaction time is increased from 0.5 h to 2 h, the particle size enlarges from 100 to 250 nm and the Fe3O4 content decreases from 46.4% to 2.6%. The thermal responses are more pronounced in the 2 h sample with the phase transition temperature (lower critical solution temperature, LCST) about 35 degrees C. The nanoparticles show a gradient concentration distribution of AAc as the particles propagate. A higher AAc concentration is observed near'the Fe3O4 core and the AAc content deceases as the degree of polymerization increases in the latex particles. This declining AAc concentration is beneficial for profound thermal responses in the synthesized nanoparticle.

Time-resolved polymer propagation for acrylic acid-mediated nanolatexes containing magnetic Fe3O4 cores.

We simultaneously employed grazing incidence small-angle and wide-angle X-ray scattering (GISAXS and GIWAXS) techniques to quantitatively study the structural evolution and kinetic behavior of poly(3-hexylthiophene) (P3HT) crystallization, [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) aggregation and amorphous P3HT/PCBM domains from a bulk heterojunction (BHJ) to a thermally unstable structure. The independent phase separation regimes on the nanoscale (∼10 nm), mesoscale (∼100 nm) and macroscale (∼μm) are revealed for the first time. Bis-PCBM molecules as inhibitors incorporated into the P3HT/PCBM blend films were adopted as a case study of a control strategy for improving the thermal stability of P3HT/PCBM solar cell. The detailed information on the formation, growth, transformation and mutual interaction between different phases during the hierarchical structural evolution of P3HT/PCBM:xbis-PCBM (x = 8-100%) blend films are presented herein. This systematic study proposes the mechanisms of thermal instability for a polymer/fullerene-based solar cell. We demonstrate a new fundamental concept that the structural evolution and thermal stability of mesoscale amorphous P3HT/PCBM domains during heating are the origin of controlling thermal instability rather than those of nanoscale thermally-stable BHJ structures. It leads to a low-cost and easy-fabrication control strategy for effectively tailoring the hierarchical morphology against thermal instability from molecular to macro scales. The optimum treatment achieving high thermal stability, control of mesoscale domains, can be effectively designed. It is independent of the original BHJ nanostructure design of a polymer/fullerene-based solar cell with high performance. It advances the general knowledge on the thermal instability directly arising from the nanoscale structure.

Mechanism and control of the structural evolution of a polymer solar cell from a bulk heterojunction to a thermally unstable hierarchical structure.

Thermo-sensitive poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAAm-co-AAc)) latex particles were prepared with and without sodium dodecyl sulfate (SDS) surfactant via an emulsion polymerization method. The P(NIPAAm-co-AAc) latex particle sizes were approximately 1.1 microm without SDS addition and the particle sizes were in the nanometer range (59 nm) with SDS at its critical micelle concentration (CMC) of 8 mM. We propose a scheme to demonstrate how the SDS concentration affects the synthesized latex particle size. The lower critical solution temperature (LCST) was hardly influenced by the SDS level but increased with the AAc concentration. The PNIPAAm-co-AAc latex particles were employed as thermo-sensitive drug carriers and 4-acetamidophenol was loaded to study the drug release rates from the nano-gels. The effective drug diffusion coefficients within the nano-gels varied as a function of particle size, AAc content, and temperature. The smaller or AAc-rich hydrogel particles provided sustainable drug release property and have potential use in biomedical applications.

Micron- and nano-sized poly(N-isopropylacrylamide-co-acrylic acid) latex syntheses and their applications for controlled drug release.

In the present work, we prepare thermo- and pH-sensitive polymer-based nanoparticles incorporating with magnetic iron oxide as the remote-controlled, stimuli-response nanocarriers. Well-defined, dual functional tri-block copolymer poly[(acrylic acid)-block-(N-isopropylacrylamide)-block-(acrylic acid)], was synthesized via reversible addition-fragmentation chain-transfer (RAFT) polymerization with S,S'-bis(α,α'-dimethyl-α″-acetic acid)trithiocarbonate (CMP) as a chain transfer agent (CTA). With the aid of using 3-aminopropyltriethoxysilane, the surface-modified iron oxides, Fe3O4-NH2, was then attached on the surface of self-assembled tri-block copolymer micelles via 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride/N-hydroxysuccinamide (EDC/NHS) crosslinking method in order to furnish not only the magnetic resources for remote control but also the structure maintenance for spherical morphology of our nanocarriers. The nanocarrier was characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), and ultraviolet-visible (UV/Vis) spectral analysis. Rhodamine 6G (R6G), as the modeling drugs, was encapsulated into the magnetic nanocarriers by a simple swelling method for fluorescence-labeling and controlled release monitoring. Biocompatibility of the nanocarriers was studied via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which revealed that neither the pristine nanocarrier nor the R6G-loaded nanocarriers were cytotoxic to the normal fibroblast cells (L-929 cells). The in vitro stimuli-triggered release measurement showed that the intelligent nanocarriers were highly sensitive to the change of pH value and temperature rising by the high-frequency magnetic field (HFMF) treatment, which provided the significant potential to apply this technology to biomedical therapy by stimuli-responsive controlled release.

Self-assembly behaviors of thermal- and pH- sensitive magnetic nanocarriers for stimuli-triggered release.

The effects of the spatial arrangement of the conjugated side chains of two-dimensional polymers on their optical, electrochemical, molecular-packing, and photovoltaic characteristics were investigated. Accordingly, novel polythiophenes with horizontally (PBTTTV-h) and vertically (PBTTTV-v) grafted terthiophene–vinylene (TTV) conjugated side chains were synthesized that display two and one UV-vis peaks, respectively; the difference is due to the different constitutions of the conjugated side-chains. Because the spatial arrangement affects the molecular self-assembly, PBTTTV-h shows stronger crystallinity than PBTTTV-v, which enhances the charge mobility in devices. Moreover, PBTTTV-h has a lower HOMO energy level (−5.49 eV) than PBTTTV-v (−5.40 eV). Bulk heterojunction solar cells fabricated from PBTTTV-h/PC71BM and PBTTTV-v/PC71BM exhibit power conversion efficiencies of 4.75% and 4.00%, respectively, and Voc values of 800 and 730 mV, respectively, under AM1.5G illumination (100 mW cm(−2)). Thus, the architecture of the TTV conjugated side chains affects the optical, electrochemical, and photovoltaic properties; this study provides more ideas for improving 2-D conjugated polymers for semiconductor devices.

Impact of constitution of the terthiophene-vinylene conjugated side chain on the optical and photovoltaic properties of two-dimensional polythiophenes.

Environmentally sensitive composite nanofibrous mats capable of metal ion adsorption were successfully prepared via electrospinning. The composite nanofibers were fabricated with different ratios of chitosan to thermo-responsive polymer, poly(N-isopropylacrylamide-co-N-methylolacrylamide) (poly(NIPAAm-co-NMA), PNN). NMA provided the function of thermal crosslinking of the nanofibrous mats to form water-stable nanofibers in aqueous solution. Subsequently, glutaraldehyde was used as a secondary crosslinking agent to increase the gel fraction of the nanofibrous mats. The morphology changes of the nanofibers in different environments were studied. Comparing the nanofibrous mats and films of the same material, the fibrous mats showed significantly increased adsorption of Cu(II). The adsorption amount of Cu(II) on the chitosan/PNN (50/50) nanofibrous mats could reach 79±2 mg/g-mats, and its desorption was relatively effective. The incorporation of poly(NIPAAm-co-NMA) significantly improved the desorption of Cu(II) from the nanofibrous mats. The chitosan/PNN fibrous mats maintained the capacity of Cu(II) adsorption for 4-time regeneration.

Evaluation of thermally crosslinkable chitosan-based nanofibrous mats for the removal of metal ions.

Magnetic silica core/shell nanovehicles presenting atherosclerotic plaque-specific peptide-1 (AP-1) as a targeting ligand (MPVA-AP1 nanovehicles) have been prepared through a double-emulsion method and surface modification. Amphiphilic poly(vinyl alcohol) was introduced as a polymer binder to encapsulate various drug molecules (hydrophobic, hydrophilic, polymeric) and magnetic iron oxide (Fe3O4) nanoparticles. Under a high-frequency magnetic field, magnetic carriers (diameter: ca. 50 nm) incorporating the anti-cancer drug doxorubicin collapsed, releasing approximately 80% of the drug payload, due to the heat generated by the rapidly rotating Fe3O4 nanoparticles, thereby realizing rapid and accurate controlled drug release. Simultaneously, the magnetic Fe3O4 themselves could also kill the tumor cells through a hyperthermia effect (inductive heating). Unlike their ungrafted congeners (MPVA nanovehicles), the AP1-grafted nanovehicles bound efficiently to colorectal cancer cells (CT26-IL4Rα), thereby displaying tumor-cell selectivity. The combination of remote control, targeted dosing, drug-loading flexibility, and thermotherapy and chemotherapy suggests that magnetic nanovehicles such as MPVA-AP1 have great potential for application in cancer therapy.

Article	Year
Preparation of thermoresponsive core-shell copolymer latex with potential use in drug targeting. Journal of colloid and interface science\| PubMed ID: 15946672	2005
Preparation and properties of poly(acrylic acid) oligomer stabilized superparamagnetic ferrofluid. Journal of colloid and interface science\| PubMed ID: 16009367	2005
Structure and polymer form of poly-3-hydroxyalkanoates produced by Pseudomonas oleovorans grown with mixture of sodium octanoate/undecylenic acid and sodium octanoate/5-phenylvaleric acid. International journal of biological macromolecules\| PubMed ID: 16919325	2007
Synthesis of nano-sized TiO(2)/poly(AA-co-MMA) composites by heterocoagulation and blending with PET. Journal of colloid and interface science\| PubMed ID: 17250847	2007
P(AA-SA) latex particle synthesis via inverse miniemulsion polymerization-nucleation mechanism and its application in pH buffering. Journal of colloid and interface science\| PubMed ID: 18990405	2009
Controlling formation of silver/carbon nanotube networks for highly conductive film surface. ACS applied materials & interfaces\| PubMed ID: 22301712	2012
Time-resolved polymer propagation for acrylic acid-mediated nanolatexes containing magnetic Fe3O4 cores. Journal of nanoscience and nanotechnology\| PubMed ID: 23755658	2013
Mechanism and control of the structural evolution of a polymer solar cell from a bulk heterojunction to a thermally unstable hierarchical structure. Nanoscale\| PubMed ID: 23846751	2013
Micron- and nano-sized poly(N-isopropylacrylamide-co-acrylic acid) latex syntheses and their applications for controlled drug release. Journal of nanoscience and nanotechnology\| PubMed ID: 23882758	2013
Self-assembly behaviors of thermal- and pH- sensitive magnetic nanocarriers for stimuli-triggered release. Nanoscale research letters\| PubMed ID: 25288914	2014
Impact of constitution of the terthiophene-vinylene conjugated side chain on the optical and photovoltaic properties of two-dimensional polythiophenes. Physical chemistry chemical physics : PCCP\| PubMed ID: 25332133	2014
Evaluation of thermally crosslinkable chitosan-based nanofibrous mats for the removal of metal ions. Carbohydrate polymers\| PubMed ID: 25458297	2015
Magnetically triggered nanovehicles for controlled drug release as a colorectal cancer therapy. Colloids and surfaces. B, Biointerfaces\| PubMed ID: 26705859	2016

Wen-Yen Chiu

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