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Using machine learning based on a random forest (RF) regression algorithm, we attempted to predict the amount of adsorbed serum protein on polymer brush films from the films' physicochemical information and the monomers' chemical structures constituting the films using a RF model. After the training of the RF model using the data of polymer brush films synthesized from five different types of monomers, the model became capable of predicting the amount of adsorbed protein from the chemical structure, physicochemical properties of monomer molecules, and structural parameters (density and thickness of the films). The analysis of the trained RF quantitatively provided the importance of each structural parameter and physicochemical properties of monomers toward serum protein adsorption (SPA). The ranking for the significance of the parameters agrees with our general understanding and perception. Based on the results, we discuss the correlation between brush film's physical properties (such as thickness and density) and SPA and attempt to provide a guideline for the design of antibiofouling polymer brush films.

Water molecules play a crucial role in biointerfacial interactions, including protein adsorption and desorption. To understand the role of water in the interaction of proteins and cells at biological interfaces, it is important to compare particular states of hydration water with various physicochemical properties of hydrated biomaterials. In this review, we discuss the fundamental concepts for determining the interactions of proteins and cells with hydrated materials along with selected examples corresponding to our recent studies, including poly(2-methoxyethyl acrylate) (PMEA), PMEA derivatives, and other biomaterials. The states of water were analyzed by differential scanning calorimetry, in situ attenuated total reflection infrared spectroscopy, and surface force measurements. We found that intermediate water which is loosely bound to a biomaterial, is a useful indicator of the bioinertness of material surfaces. This finding on intermediate water provides novel insights and helps develop novel experimental models for understanding protein adsorption in a wide range of materials, such as those used in biomedical applications., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Amphiphilic diblock copolymers are prepared by ring opening metathesis polymerization, with one block containing hydrophobic Toll-like receptor 7 (TLR7) agonists and one block containing hydrophilic peptides as substrates for matrix metalloproteinases (MMPs). A fluorescent label is incorporated into the polymer chains for in vivo imaging. Upon dialysis against aqueous solution, polymers form 15 nm spherical micelles. Subsequent exposure to MMP-9 elicits a morphological change to yield immunostimulatory microscale assemblies. The intravenous (IV) administration of the formulation to mice bearing 4T1 breast cancer tumors results in nanoparticle accumulation in tumors, reduction in primary tumor growth, and inhibition of lung metastases, as compared to saline-treated animals. Mice administered the parent immunotherapeutic small molecule (1V209) experience significantly increased plasma levels of proinflammatory cytokines IL-6, IP-10, and MCP-1 at 2 h following IV administration, whereas the nanomaterial shows no increase over saline-treated controls. These data suggest that covalently packaging low molecular weight immunotherapeutics at high weight percent loadings in enzyme-responsive nanoparticles maintains drug efficacy while decreasing immunotoxicity, providing a platform for cancer immunotherapeutic delivery., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Engineered variants of the capsid-forming enzyme lumazine synthase, AaLS, were used as nanoreactors for an enzyme-mediated polymerization. Oxidation of 3,3-diaminobenzidine (DAB) by the engineered ascorbate peroxidase APEX2 encapsulated in AaLS capsids resulted in templated formation of polyDAB-capsid nanoparticles of homogeneous size and shape.

A supramolecular conjugate of myoglobin (Mb) and water-soluble poly(acrylate), (PA5k and PA25k , where 5k and 25k represent the molecular weight of the polymers, respectively), is constructed on the basis of a noncovalent heme-heme pocket interaction. The modified heme with an amino group linked to the terminus of one of the heme-propionates is coupled to the side-chain carboxyl groups of poly(acrylate) activated by N-hydroxysuccinimide. The ratios of the heme-modified monomer unit and the unmodified monomer unit (m:n) in the polymer chains of Heme-PA5k and Heme-PA25k were determined to be 4.5:95.5 and 3.1:96.9, respectively. Subsequent addition of apoMb to the conjugated polymers provides Mb-connected fibrous nanostructures confirmed by atomic force microscopy. A mixture of the heme-modified polymer and dimeric apomyoglobin as a cross-linker forms a microgel in which the reconstituted myoglobin retains its native exogenous ligand binding activity., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Two luminescent porous coordination polymers (PCPs), i.e., [Cu2(μ2-I)2ctpyz]n and [Cu4(μ3-I)4ctpyz]n (Cu2 and Cu4, respectively; ctpyz = cis-1,3,5-cyclohexanetriyl-2,2',2″-tripyrazine), were successfully synthesized and characterized by single-crystal X-ray diffraction and luminescence spectroscopic measurements. Cu2 consists of rhombus-type dinuclear {Cu2I2} cores bridged by ctpyz ligands, while Cu4 is constructed of cubane-type tetranuclear {Cu4I4} cores bridged by ctpyz ligands. The void fraction of Cu4 is estimated to be 48.0%, which is significantly larger than that of Cu2 (19.9%). Under UV irradiation, both PCPs exhibit red luminescence at room temperature in the solid state (λem values of 660 and 614 nm for Cu2 and Cu4, respectively). Although the phosphorescence of Cu2 does not change upon removal and/or adsorption of EtOH solvent molecules in the porous channels, the solid-state emission maximum of Cu4 red-shifts by 36 nm (λem = 650 nm) upon the removal of the adsorbed benzonitrile (PhCN) molecules from the porous channels (and vice versa). This large difference in the vapochromic behavior of Cu2 and Cu4 is closely related to the framework flexibility. The framework of Cu2 is sufficiently rigid to retain the porous structure without solvated EtOH molecules, whereas the porous structure of Cu4 collapses easily after removal of the adsorbed PhCN molecules to form a nonporous amorphous phase. The original vapor-adsorbed porous structure of Cu4 is regenerated by exposure of the amorphous solid to not only PhCN vapor but also tetrahydrofuran, acetone, ethyl acetate, and N,N-dimethylformamide vapors. The Cu4 structures with the various adsorbed solvents showed almost the same emission maxima as the original PhCN-adsorbed Cu4, except for DMF-adsorbed Cu4, which showed no luminescence probably because of weak coordination of the DMF vapor molecules to the Cu(I) centers of the tetranuclear {Cu4I4} core.

We developed new cationic fluorescent polymeric thermometers containing both benzothiadiazole and BODIPY units as an environment-sensitive fluorophore and as a reference fluorophore, respectively. The temperature-dependent fluorescence spectra of the thermometers enabled us to perform highly sensitive and practical ratiometric temperature sensing inside living mammalian cells. Intracellular temperatures of non-adherent MOLT-4 (human acute lymphoblastic leukaemia) and adherent HEK293T (human embryonic kidney) cells could be monitored with high temperature resolutions (0.01-1.0 °C) using the new cationic fluorescent polymeric thermometer.

Changes in intracellular temperatures reflect the activity of the cell. Thus, the tool to measure intracellular temperatures could provide valuable information about cellular status. We previously reported a method to analyze the intracellular temperature distribution using a fluorescent polymeric thermometer (FPT) in combination with fluorescence lifetime imaging microscopy (FLIM). Intracellular delivery of the FPT used in the previous study required microinjection. We now report a novel FPT that is cell permeable and highly photostable, and we describe the application of this FPT to the imaging of intracellular temperature distributions in various types of mammalian cell lines. This cell-permeable FPT displayed a temperature resolution of 0.05°C to 0.54°C within the range from 28°C to 38°C in HeLa cell extracts. Using our optimized protocol, this cell-permeable FPT spontaneously diffused into HeLa cells within 10 min of incubation and exhibited minimal toxicity over several hours of observation. FLIM analysis confirmed a temperature difference between the nucleus and the cytoplasm and heat production near the mitochondria, which were also detected previously using the microinjected FPT. We also showed that this cell-permeable FPT protocol can be applied to other mammalian cell lines, COS7 and NIH/3T3 cells. Thus, this cell-permeable FPT represents a promising tool to study cellular states and functions with respect to temperature.

In order to create suitable biocompatible materials for various tissue engineering applications, it is important to be able to understand protein adsorption and cell adhesion behaviors on the material's surfaces. It is known that the nanoscale distribution of adsorbed proteins affects cell adhesion behaviors. However, how nanoscale structures affect cell adhesion behaviors is still unclear. Therefore, in this study, we investigate the effect of the distribution of adsorbed proteins by the phase reversal of amphiphilic block copolymers composed of protein-non-adsorptive poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and protein-adsorptive poly(3-methacryloyloxy propyltris(trimethylsilyloxy) silane) (PMPTSSi) on cell adhesion behaviors. The nanodomain structures of phase-separated block copolymers were successfully confirmed using transmission electron microscopy and atomic force microscopy. Surfaces that had PMPC dot-like domains (23 ± 4 nm) and ones that had PMPTSSi dot-like domains (25 ± 6 nm) were made. From protein adsorption and L929 cell adhesion measurements, it was found that even on surfaces with equal quantities of protein adsorption, the number of cells on surfaces with PMPC dot-like domains was larger than those with PMPTSSi dot-like domains. This suggests that the simple phase-reversal of the distribution of adsorbed proteins can be used to affect cell adhesion behaviors for designing biomaterial surfaces for tissue engineering applications., (Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Ultrasound compaction is a simple small-scale heating process. The aim of this study was to elucidate the polymer phase transition process during ultrasound compaction by process monitoring. Morphological change with heat occurs when ultrasound energy is supplied. Monitoring of the process revealed changes in both punch position and the pressure of the die in terms of the polymer's phase transition process. The optimum ultrasound energy for complete transition could be detected by a sudden increase in the pressure on the lower punch. Such optimum energy clearly depended on the polymer's glass transition temperature (Tg), suggesting that Tg is the predominant parameter in the ultrasound compaction process. Optimization of ultrasound energy based on monitoring profiles is a promising way to obtain a desirable product by thermoplastic treatment with minimal thermal degradation due to excess supply of energy., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Ferritin grafted with temperature-responsive poly(N-isopropylacrylamide) (PIPAAm-ferritin) was synthesized by a coupling reaction using PIPAAm and ferritin for obtaining stimuli-responsive biomaterials. The hydrodynamic diameter of PIPAAm-ferritins in aqueous solution increased at 37 °C at a higher protein concentration (>0.2mg/mL) because of the intermolecular aggregation through the hydrophobic interaction of PIPAAm chains. On the other hand, PIPAAm-ferritins at a lower concentration (<0.2mg/mL) were unable to increase their size even at 37 °C. The adsorption kinetics of PIPAAm-ferritins on hydrophobically modified Si substrate were evaluated with a quartz crystal microbalance in 10 mmol/L Bis-Tris/HCl buffer (pH 5.8) with and without poly(oxyethylene) sorbitan monolaurate (TWEEN 20) (0.05 wt%) as a surfactant. Although the adsorption of PIPAAm-ferritins on hydrophobic Si substrate at 25 °C in the buffer with TWEEN 20 was hardly observed, PIPAAm-ferritins were considerably adsorbed on the substrate at 37 °C, indicating that the hydrophobic interaction between the substrate and PIPAAm grafts on the ferritins after the destruction of the hydrophobic interaction between the protein and the substrate by TWEEN 20., (Copyright © 2012 Elsevier B.V. All rights reserved.)

We compared the in vitro/in vivo properties of theophylline between two sustained-release preparations, which are administered once a day. Tablet A is a swelling/disintegration-type matrix tablet consisting of hydrophobic wax granules and hydrophilic polymer granules (cluster tablets). Tablet B is a matrix tablet consisting of hydrophilic polymer granules. We conducted a dissolution test with JPXIV in vitro, and compared the results between the two preparations. Neither pH nor agitation intensity influenced these preparations. After they were immersed in oleic acid, there were no marked changes in the dissolution properties in the dissolution test. After administration of Tablets A and B containing theophylline at 200mg to fasted dogs, we compared plasma level profiles of theophylline. The mean plasma level of theophylline gradually increased to a maximum (7.17microg/mL) 4h after administration of Tablet A. After administration of Tablet B, a similar finding was noted, with a maximum of 6.09microg/mL. Tablet B showed a higher coefficient of variation (CV) for the plasma level at each point. Subsequently, we administered two tablets of preparations A and B containing theophylline at 200mg to healthy volunteers who had not been fasted, and compared plasma level concentration of theophylline. The mean plasma level of theophylline gradually increased to a maximum (6.09microg/mL) 12h after administration of Tablet A, but then decreased, with a half-life of 9.10h. After administration of Tablet B, a similar finding was noted, with a maximum of 7.87microg/mL and a half-life of 7.76h. Tablet A showed a significantly higher plasma concentration 1 and 2h after administration; however, there were no significant differences at other points. The C(max) of Tablet B was significantly higher than that of Tablet A. However, there were no significant differences in other pharmacokinetic parameters between the two preparations. The T(max) of Tablet A was 10-12h after administration, relatively constant. However, that of Tablet B was 10-18h after administration. The CV for T(max) was 9.8% for Tablet A and 22.0% for Tablet B. After administration of Tablet B, the plasma level of theophylline varied at each point. Based on these results, inter-subject variations after administration of Tablet A may be less marked than those after administration of Tablet B. It is concluded that, the cluster tablets A developed in this study showed significantly less inter-subject variation of theophylline plasma levels than the conventional matrix tablets B.

Honeycomb-patterned films have been reported to be useful for scaffolds of cell culture in tissue engineering. In the present study, we investigated a new compound, dioleoylphosphatidylethanolamine (DOPE), a naturally derived phospholipid having unsaturated fatty acid moieties, as a surfactant for fabricating honeycomb-patterned poly(d,l-lactide) (PLA) film. Only DOPE among commercially available phospholipids was useful as a surfactant, and it showed good solubility in PLA/chloroform solution and an excellent property for fabricating honeycomb-patterned film (the concentration of DOPE was from 0.2% to 20% by weight based on the weight of PLA). The pore size of the honeycomb was uniform, and all pores were interconnected with each other. The contact angle of water on the honeycomb-patterned film was affected by the amount of DOPE. Time-of-flight secondary ion mass spectrometer (TOF-SIMS) data suggested that DOPE was concentrated on the surface of the honeycomb-patterned film. To investigate cell proliferation and adhesion on the honeycomb-patterned film, NIH3T3 fibroblast cells were cultured on the film. The NIH3T3 cells adhered well on the honeycomb-patterned PLA film with DOPE (PLA-DOPE) and showed good cell proliferation compared to that on honeycomb-patterned PLA film fabricated with a copolymer (CAP) of dodecylacrylamide and omega-carboxyhexylacrylamide (PLA-CAP). These results suggest that the honeycomb-patterned PLA-DOPE can be applicable as a scaffold for cells with better profiles in comparison with PLA-CAP.

Two matrix theophylline tablets with different release mechanisms were compared. Tablet A was a swelling/disintegration-type wax matrix made of hydrophobic wax granules, consisting of stearic acid, hydrogenated oil and glycerol esters of fatty acids, and hydrophilic polymer granules composed primarily of hydroxypropyl methylcellulose (HPMC). We named Tablet A the cluster tablet. Tablet B was a gel matrix made of hydrophobic ethylcellulose granules, consisting of ethylcellulose and hydrogenated oil, and hydrophilic polymer granules consisting of HPMC and hydroxylpropylmethylcellulose acetate succinate (HPMCAS). The formulations were screened in vitro according to their dissolution characteristics. The drug release from each preparation was analyzed using release kinetics theories. In Tablet A, the value of the exponent(n) representing the apparent diffusion mechanism determined from the Korsmeyer-Peppas model equation was about 0.6 and was unlikely to be affected by the rotation speed. In Tablet B, the value of the exponent(n) by the Korsmeyer-Peppas model equation changed with the paddle rotation speed. These results suggested that the drug release mechanism of Tablet B is greatly affected by the extent of physical force in the gastrointestinal tract.

Molecularly imprinted polymer (MIP) was prepared against phenobarbital using methacrylic acid as the functional monomer and ethylene glycol dimethacrylate as the cross linking monomer. We analyzed the recognition properties of the phenobarbital MIP. In some organic solvents, imprinted polymer showed selective binding to phenobarbital. Two dissociation constants of binding were calculated by Scatchard plot analyses; Kd values were 1.8, 121.7 microM, and the number of binding sites was 8.3, 92.3 mumol/g MIP in toluene-heptane-acetic acid (25 : 75 : 1, v/v), respectively. The relationship between the binding affinity to phenobarbital MIP and the polarity of the solvent system, as well as the structure of the template molecule is also discussed.

The surface characteristics of A-B-A type triblock copolymer (GIG) membranes consisting of alpha-helical poly (gamma-benzyl-L-glutamate) (PBLG) as the A component and polyisoprene (PI) as the B component were investigated by X-ray photoelectron spectroscopy (XPS) and contact angle measurements. The XPS measurements showed the copolymer composition of the outermost surface to be quite different from the bulk composition. Results of contact angle measurements indicated the existence of an interfacial region between the alpha-helical A component and the B component at the surfaces of the block copolymer membranes. Finally, the results of in vivo tests on tissue compatibility indicate that the GIG block copolymer membranes have good biocompatibility.

Residual monomers in resin-based biomaterials cause cytotoxicity. We previously showed that methyl methacrylate (MMA) induced mRNA expression of the glutathione S-transferase alpha 1 gene (Gsta1) located downstream of the cis-acting anti-oxidant responsive element (ARE). Herein, we tested the hypothesis that MMA activated the Gsta1 promoter through the ARE. HepG2 cells were transfected with a luciferase reporter vector containing the ARE and the Gsta1 promoter (-990 to +46 bp) and cultured for 12 hrs with MMA (initial concentration, 10 mM). Analysis of the expressed luciferase activity indicated that MMA activated the promoter 2.6-fold. MMA (from 1 to 30 mM) dose-dependently increased the promoter activity, which reached a plateau between 6 and 12 hrs. In HepG2 cells transfected with a reporter vector containing 2 AREs and a TATA-like promoter, 10 mM MMA increased the reporter expression 2.8-fold. These results suggest that MMA increases Gsta1 transcription through ARE-mediated promoter activation. Abbreviations: ANOVA, analysis of variance; ARE, anti-oxidant responsive element; Gsta1, mouse glutathione S-transferase alpha 1 gene; GSH, glutathione; GST, glutathione S-transferase; Keap1, Kelch ECH associating protein 1; MMA, methyl methacrylate; NQO1, NAD(P)H:quinone oxidoreductase 1; Nrf2, nuclear factor erythroid 2-related factor 2; PCR, polymerase chain-reaction; ROS, reactive oxygen species; SEM, standard error of mean; t-BHQ, tert-butylhydroquinone. [ABSTRACT FROM AUTHOR]

In spite of the clinical usefulness of cisplatin (CDDP), there are many occasions in which it is difficult to continue the administration of CDDP due to its nephrotoxicity and neurotoxicity. We examined the incorporation of CDDP into polymeric micelles to see if this allowed the resolution of these disadvantages. Cisplatin was incorporated into polymeric micelles through the polymer–metal complex formation between polyethylene glycol poly(glutamic acid) block copolymers and CDDP (NC-6004). The pharmacokinetics, pharmacodynamics, and toxicity studies of CDDP and NC-6004 were conducted in rats or mice. The particle size of NC-6004 was approximately 30 nm, with a narrow size distribution. In rats, the area under the curve and total body clearance values for NC-6004 were 65-fold and one-nineteenth the values for CDDP (P<0.001 and 0.01, respectively). In MKN-45-implanted mice, NC-6004 tended to show antitumour activity, which was comparable to or greater than that of CDDP. Histopathological and biochemical studies revealed that NC-6004 significantly inhibited the nephrotoxicity of CDDP. On the other hand, blood biochemistry revealed transient hepatotoxicity on day 7 after the administration of NC-6004. Furthermore, rats given CDDP showed a significant delay (P<0.05) in sensory nerve conduction velocity in their hind paws as compared with rats given NC-6004. Electron microscopy in rats given CDDP indicated the degeneration of the sciatic nerve, but these findings were not seen in rats given NC-6004. These results were presumably attributable to the significantly reduced accumulation of platinum in nerve tissue when NC-6004 was administered (P<0.05). NC-6004 preserved the antitumour activity of CDDP and reduced its nephrotoxicity and neurotoxicity, which would therefore seem to suggest that NC-6004 could allow the long-term administration of CDDP where caution against hepatic dysfunction must be exercised.British Journal of Cancer (2005) 93, 678–687. doi:10.1038/sj.bjc.6602772 www.bjcancer.com published online 13 September 2005 [ABSTRACT FROM AUTHOR]

Examines the transient absorbance of doped poly(methyl methacrylate) with pyrene or biphenyl polymers. Calculation of excitation wavelength at laser ablation conditions; Changes in absorbance due to transient species and scattering by ablated fragments; Number of photons absorbed in doped polymer films.

We review the latest advances in the production and state-of-the art characterization of B- and N-doped carbon nanotubes (CNTs) and nanofibers. We briefly discuss different approaches to producing these novel doped nano-systems. The use of high-resolution transmission electron microscopy (HRTEM), electron energy loss spectroscopy (EELS), scanning tunneling spectroscopy (STS), Raman spectroscopy, and allied techniques to characterize these doped systems is reviewed. The field emission properties as well as some applications to the fabrication of novel polymer composites, Li+ batteries, and gas sensors are also discussed. It is clear that these materials possess outstanding properties when compared with pure CNTs, and it is foreseen that these systems will revolutionize some aspects of nanotube science and technology, thus opening a vast field of experimental and theoretical research. [Copyright &y& Elsevier]