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 steady directional EOF due to a nonlinear interaction between oscillatory axial electrical fields and oscillatory wall potentials (zeta potentials) is presented. This is a new mechanism to produce such a mean flow. It is found that the flow velocity depends not on the external driving frequency but on the phase angle difference between the electric fields and the zeta potentials. The formulation can also be reduced to the static EOF straightforwardly. For the purpose of theoretical demonstration, we use the Debye-Huckel approximation for the zeta potential. Results of planar and cylindrical capillaries are given.

Generation of directional EOF by interactive oscillatory zeta potential.

The electro-osmotic flow driven by a screen pump, composed of a line array of evenly spaced identical rectangular solid blocks, is investigated under the Debye-Hückel approximation. The geometry of the screen pump is determined by the spacing and aspect ratio of the solid blocks. A constant surface zeta potential is assumed on the block surface. The method of eigenfunction series expansion is applied to solve analytically for the applied electric field, electric charge potential in the fluid, and flow field. Because of the low Reynolds number, Stokes equations are applied for the flow. The analytic result is first confirmed by comparing with the exact solution of the electro-osmotic flow in an infinite channel. Then different geometries of the screen pump and the effect of the electrokinetic width are computed for their influence on the flow rate. Recirculating eddies and reversing flow are found even though the applied electric driving field is unidirectional.

Electro-osmotic flow through a two-dimensional screen-pump filter.

The present study is concerned with unsteady electroosmotic flow (EOF) in a microchannel with the electric charge distribution described by the Poisson-Boltzmann (PB) equation. The nonlinear PB equation is solved by a systematic perturbation with respect to the parameter λ which measures the strength of the wall zeta potential relative to the thermal potential. In the small λ limits (λ<1), we recover the linearized PB equation - the Debye-Hückel approximation. The solutions obtained by using only three terms in the perturbation series are shown to be accurate with errors <1% for λ up to 2. The accurate solution to the PB equation is then used to solve the electrokinetic fluid transport equation for two types of unsteady flow: transient flow driven by a suddenly applied voltage and oscillatory flow driven by a time-harmonic voltage. The solution for the transient flow has important implications on EOF as an effective means for transporting electrolytes in microchannels with various electrokinetic widths. On the other hand, the solution for the oscillatory flow is shown to have important physical implications on EOF in mixing electrolytes in terms of the amplitude and phase of the resulting time-harmonic EOF rate, which depends on the applied frequency and the electrokinetic width of the microchannel as well as on the parameter λ.

Unsteady electroosmosis in a microchannel with Poisson-Boltzmann charge distribution.

In this study, we developed the cancer treatment through the combination of chemotherapy and thermotherapy using doxorubicin-loaded magnetic liposomes. The citric acid-coated magnetic nanoparticles (CAMNP, ca. 10 nm) and doxorubicin were encapsulated into the liposome (HSPC/DSPE/cholesterol = 12.5:1:8.25) by rotary evaporation and ultrasonication process. The resultant magnetic liposomes (ca. 90 to 130 nm) were subject to characterization including transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), zeta potential, Fourier transform infrared (FTIR) spectrophotometer, and fluorescence microscope. In vitro cytotoxicity of the drug carrier platform was investigated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using L-929 cells, as the mammalian cell model. In vitro cytotoxicity and hyperthermia (inductive heating) studies were evaluated against colorectal cancer (CT-26 cells) with high-frequency magnetic field (HFMF) exposure. MTT assay revealed that these drug carriers exhibited no cytotoxicity against L-929 cells, suggesting excellent biocompatibility. When the magnetic liposomes with 1 μM doxorubicin was used to treat CT-26 cells in combination with HFMF exposure, approximately 56% cells were killed and found to be more effective than either hyperthermia or chemotherapy treatment individually. Therefore, these results show that the synergistic effects between chemotherapy (drug-controlled release) and hyperthermia increase the capability to kill cancer cells.

Magnetic liposomes for colorectal cancer cells therapy by high-frequency magnetic field treatment.

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.

We investigate the basic features of wave propagation in bianisotropic metamaterials characterized by asymmetric magnetoelectric tensors with zero diagonal elements. The wave propagation is described by a biquadratic dispersion relation with two elliptically polarized eigenwaves. In particular, the bianisotropic media may possess a hybrid character of the elliptic and hyperbolic dispersions. For a wave incident from vacuum onto a bianisotropic medium, there exist an ordinary and an inversion critical angle, leading to angular selective transmission. A standard and a complementary type of angular selective transmissions are illustrated with the incidence of Gaussian beams based on Fourier integral formulation.

Wave propagation in bianisotropic metamaterials: angular selective transmission.

The role played by hemostasis in the pathogenesis of ischemic stroke is still controversial. In the present study, we looked for a possible association of ischemic stroke with the high clotting activity of factor VIII (FVIII). The study population consisted of 116 patients with acute ischemic stroke who had been admitted between September 2013 and September 2014 to the Department of Neurology, Chiayi Chang Gung Memorial Hospital, and 76 control subjects with no history of stroke. FVIII levels were higher in stroke patients as compared to controls (127.5 ± 52.5 vs. 108.4 ± 49.0 IU/dL; P = 0.012). In a univariate risk analysis, FVIII at levels above 150 IU/dL was associated with an odds ratio (OR) for ischemic stroke of up to 2.55 (95% CI, 1.20-5.42, P = 0.013). In a multivariate analysis using a logistic regression model including age, hypertension, low density lipoprotein cholesterol level, estimated glomerular filtration rate, and high FVIII (< 150 IU/dL), high FVIII was still found to significantly add to the risk of ischemic stroke (OR = 3.26 with 95% CI, 1.38-7.68, P = 0.007). As for the stroke subtypes, mean FVIII level was significantly higher in patients with cardioembolic stroke than patients with noncardioembolic stroke (156.0 ± 51.5 IU/dL vs. 124.3 ± 51.9 IU/dL). High levels of FVIII were also associated significantly with neurological worsening (OR = 3.66 with 95% CI, 1.24-10.82, P = 0.019). A high plasma level of FVIII is a prevalent and independent risk factor for ischemic stroke and neurological worsening after acute stroke.

Factor VIII levels are associated with ischemic stroke, stroke subtypes and neurological worsening.

The role played by hemostasis in the pathogenesis of ischemic strokes is still controversial. The activated partial thromboplastin time (APTT) measures the time necessary to generate fibrin from initiation of the intrinsic pathway. In the present study, we looked for a possible association of ischemic strokes with the shortened APTT.

Shortened Activated Partial Thromboplastin Time Is Associated With Acute Ischemic Stroke, Stroke Severity, and Neurological Worsening.

In this study, multifunctional hybrid nanoparticles composed of iron platinum (FePt), silica (SiO2), and gold nanoparticles (AuNPs) had been developed for surface-enhanced Raman scattering (SERS) application. Core-shell structure of SiO2 and FePt nanoparticles (FePt@SiO2) was fabricated through sol-gel process and then immobilized gold nanoparticles onto the surface of FePt@SiO2, which displays huge Raman enhancement effect and magnetic separation capability. The resulting core-shell nanoparticles were subject to evaluation by transmission electron microscopy (TEM), Energy-dispersive X-ray spectroscopy (EDX), zeta potential measurement, and X-ray photoelectron spectroscopy (XPS). TEM observation revealed that the particle size of resultant nanoparticles displayed spherical structure with the size ~30 nm and further proved the successful immobilization of Au onto the surface of FePt@SiO2. Zeta potential measurement exhibited the successful reaction between FePt@SiO2 and AuNPs. The rapid SERS detection and identification of small biomolecules (adenine) and microorganisms (gram-positive bacteria, Staphylococcus aureus) was conducted through Raman spectroscopy. In summary, the novel core-shell magnetic nanoparticles could be anticipated to apply in the rapid magnetic separation under the external magnetic field due to the core of the FePt superparamagnetic nanoparticles and label-free SERS bio-sensing of biomolecules and bacteria.

Core-shell of FePt@SiO2-Au magnetic nanoparticles for rapid SERS detection.

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.

Magnetically triggered nanovehicles for controlled drug release as a colorectal cancer therapy.

Termites are a key functional group in the forest ecosystem, but they damage trees. To investigate the termite infestation pattern on the whole tree, we cut 108 blackboard trees,Alstonia scholaris(L.) R. Br., and 50 Japanese cedars,Cryptomeria japonica (L. f.) D. Don, into sections. The bark surface and cross sections of the tree trunk were examined along the axes. A high percentage of blackboard trees (92.6%) was infested by fungus-growing termites,Odontotermes formosanus(Shiraki), but damage was limited to the bark surface at a 2-m height. The infestation rate of dampwood termites,Neotermes koshunensis(Shiraki), was only 4.6% (5/108), and all infestations were associated with trunk wounds.N. koshunensiswas found at significantly higher portion of a tree thanO. formosanus Among 50 Japanese cedars, 20 living trees were not infested by any termites, but 26 of the 30 dead trees were infested by subterranean termites,Reticulitermes flaviceps(Oshima), which excavated tunnels in the trunk. The infestation rate at basal sections was higher than that at distal sections. Only one Japanese cedar tree was infested by another dampwood termite,Glyptotermes satsumensis(Matsumura). The two dominant termite species,O. formosanusandR. flaviceps, had subterranean nests and infested trees from bottom up. The two primitive termitesN. koshunensis andG. satsumensishad low infestation rates and are most likely to infest trees by alates from top down. The niche segregation in trees of three termite families, Kalotermitidae, Rhinotermitidae, and Termitidae, was distinct.

Vertical Distribution of Termites on Trees in Two Forest Landscapes in Taiwan.

The low-density lipoprotein receptor-related protein 1 (LRP1) gene is associated with increased levels of plasma factor VIII (FVIII). We aimed to explore eight functional genetic LRP1 variants for their potential roles in regulating FVIII levels and acute ischemic stroke (AIS). This genetic association study enrolled 192 patients with AIS and 134 controls. There were no significant differences in the genetic frequency of the eight functional single-nucleotide polymorphisms (SNPs) between the control and AIS groups. However, while analyzing the association between the eight SNPs and plasma FVIII levels, subjects with T/T genotype of rs1800137 (vs. CC+CT) were found to be associated with higher FVIII levels (23.5IU/dL; 95% confidence interval, 7.4-39.5IU/dL; P=0.0044) after adjusting for age, gender, estimated glomerular filtration rate, O blood type, inflammatory state, and body mass index. An analysis of the mRNA stability and abundance was designed and performed using minigene system transfected into HepG2 cells to assess the possible differences in mRNA stabilities between rs1800137 CC (rs1800137C) and TT (rs1800137T) genotypes. Site-directed mutagenesis revealed that rs1800137T accounts for the observed decrease in mRNA stability. The SNP rs1800137, located in exon 8, has been identified as an exon-splicing enhancer in silico. However, alternative splicing of LRP1 without inclusion of exon 8 was not identified. In transfected HepG2 cells, cycloheximide slowed down the degradation of the rs1800137T-containing minigene. These results demonstrate that synonymous SNP rs1800137 can lead to increased plasma FVIII levels due to decreased mRNA stability via translation-dependent mRNA degradation associated with codon optimality.

A common polymorphism decreases LRP1 mRNA stability and is associated with increased plasma factor VIII levels.

Less targeted and limited solubility of hydrophobic-based drug are one of the serious obstacles in drug delivery system. Thus, new strategies to enhance the solubility of hydrophobic drug and controlled release behaviors would be developed. Herein, curcumin, a model of hydrophobic drug, has been loaded into PEGylated magnetic liposomes as a drug carrier platform for drug controlled release system. Inductive magnetic heating (hyperthermia)-stimulated drug release, in vitro cellular cytotoxicity assay of curcumin-loaded PEGylated magnetic liposomes and cellular internalization-induced by magnetic guidance would be investigated. The resultant of drug carriers could disperse homogeneously in aqueous solution, showing a superparamagnetic characteristic and could inductive magnetic heating with external high-frequency magnetic field (HFMF). In vitro curcumin release studies confirmed that the drug carriers exhibited no significant release at 37 °C, whereas exhibited rapid releasing at 45 °C. However, it would display enormous (three times higher) curcumin releasing under the HFMF exposure, compared with that without HFMF exposure at 45 °C. In vitro cytotoxicity test shows that curcumin-loaded PEGylated magnetic liposomes could efficiently kill MCF-7 cells in parallel with increasing curcumin concentration. Fluorescence microscopy observed that these drug carriers could internalize efficiently into the cellular compartment of MCF-7 cells. Thus, it would be anticipated that the novel hydrophobic drug-loaded PEGylated magnetic liposomes in combination with inductive magnetic heating are promising to apply in the combination of chemotherapy and thermotherapy for cancer therapy.

Article	Year
Generation of directional EOF by interactive oscillatory zeta potential. Electrophoresis\| PubMed ID: 18942675	2008
Electro-osmotic flow through a two-dimensional screen-pump filter. Physical review. E, Statistical, nonlinear, and soft matter physics\| PubMed ID: 22060486	2011
Unsteady electroosmosis in a microchannel with Poisson-Boltzmann charge distribution. Electrophoresis\| PubMed ID: 22072500	2011
Magnetic liposomes for colorectal cancer cells therapy by high-frequency magnetic field treatment. Nanoscale research letters\| PubMed ID: 25246875	2014
Self-assembly behaviors of thermal- and pH- sensitive magnetic nanocarriers for stimuli-triggered release. Nanoscale research letters\| PubMed ID: 25288914	2014
Wave propagation in bianisotropic metamaterials: angular selective transmission. Optics express\| PubMed ID: 25401604	2014
Factor VIII levels are associated with ischemic stroke, stroke subtypes and neurological worsening. Current neurovascular research\| PubMed ID: 25557373	2015
Shortened Activated Partial Thromboplastin Time Is Associated With Acute Ischemic Stroke, Stroke Severity, and Neurological Worsening. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association\| PubMed ID: 26169548	2015
Core-shell of FePt@SiO2-Au magnetic nanoparticles for rapid SERS detection. Nanoscale research letters\| PubMed ID: 26489855	2015
Magnetically triggered nanovehicles for controlled drug release as a colorectal cancer therapy. Colloids and surfaces. B, Biointerfaces\| PubMed ID: 26705859	2016
Vertical Distribution of Termites on Trees in Two Forest Landscapes in Taiwan. Environmental entomology\| PubMed ID: 27016004	2016
A common polymorphism decreases LRP1 mRNA stability and is associated with increased plasma factor VIII levels. Biochimica et biophysica acta\| PubMed ID: 28431990	2017
Hydrophobic Drug-Loaded PEGylated Magnetic Liposomes for Drug-Controlled Release. Nanoscale research letters\| PubMed ID: 28525950	2017

Chih-Yu Kuo

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