Chitosan-based intelligent theragnosis nanocomposites enable pH-sensitive drug release with MR-guided imaging for cancer therapy

Smart drug delivery systems that are triggered by environmental conditions have been developed to enhance cancer therapeutic efficacy while limiting unwanted effects. Because cancer exhibits abnormally high local acidities compared to normal tissues (pH 7.4) due to Warburg effects, pH-sensitive systems have been researched for effective cancer therapy. Chitosan-based intelligent theragnosis nanocomposites, N-naphthyl-O-dimethymaleoyl chitosan-based drug-loaded magnetic nanoparticles (NChitosan-DMNPs), were developed in this study. NChitosan-DMNPs are capable of pH-sensitive drug release with MR-guided images because doxorubicin (DOX) and magnetic nanocrystals (MNCs) are encapsulated into the designed N-naphthyl-O-dimethymaleoyl chitosan (N-nap-O-MalCS). This system exhibits rapid DOX release as acidity increases, high stability under high pH conditions, and sufficient capacity for diagnosing and monitoring therapeutic responses. These results demonstrate that NChitosan-DMNPs have potential as theragnosis nanocomposites for effective cancer therapy.     

Nanostructured materials with biomimetic recognition abilities for chemical sensing

Binding features found in biological systems can be implemented into man-made materials to design nanostructured artificial receptor matrices which are suitable, e.g., for chemical sensing applications. A range of different non-covalent interactions can be utilized based on the chemical properties of the respective analyte. One example is the formation of coordinative bonds between a polymerizable ligand (e.g., N-vinyl-2-pyrrolidone) and a metal ion (e.g., Cu(II)). Optimized molecularly imprinted sensor layers lead to selectivity factors of at least 2 compared to other bivalent ions. In the same way, H-bonds can be utilized for such sensing purposes, as shown in the case of Escherichia coli. The respective molecularly imprinted polymer leads to the selectivity factor of more than 5 between the W and B strains, respectively. Furthermore, nanoparticles with optimized Pearson hardness allow for designing sensors to detect organic thiols in air. The ‘harder’ MoS₂ yields only about 40% of the signals towards octane thiol as compared to the ‘softer’ Cu₂S. However, both materials strongly prefer molecules with -SH functionality over others, such as hydrocarbon chains. Finally, selectivity studies with wheat germ agglutinin (WGA) reveal that artificial receptors yield selectivities between WGA and bovine serum albumin that are only about a factor of 2 which is smaller than natural ligands.     

Amperometric ascorbate sensor based on conducting polymer: Poly(N-methylaniline) versus polyaniline

Electrocatalytic oxidation of ascorbate (vitamin C) at poly(N-methylaniline) modified electrode has been studied and compared with that proceeding at polyaniline modified sensor. A sigmoid-shaped anodic current transient as a response to addition of ascorbate was found for polyaniline modified electrode in pH-neutral solution, whereas a ‘normal-shaped’ current transient was found to be characteristic for poly(N-methylaniline) modified electrode. Based on this, a hypothesis on the autocatalytic mechanism for electrochemical oxidation of ascorbate was confirmed. It has been shown that poly(N-methylaniline) modified electrode can be used as an amperometric ascorbate sensor, operating in slightly acidic or pH-neutral buffer solutions at a controlled potential of 0.1-0.5 V versus Ag/AgCl, and the dependencies of current response on ascorbate concentration, the thickness of a polymer layer, and operating potential have been analyzed.     

N.m.r. studies of the helix-coil transition of polypeptides in non-protonating solvent mixtures

High resolution nuclear magnetic resonance (n.m.r.) spectra have been obtained for poly(β-benzyl aspartate), poly(γ-benzyl glutamate) and several of their copolymers in the solvent system dimethylsulphoxide/chloroform, in which no amide protonation can occur. ‘Double-peak’ αCH and peptide NH resonances are observed in the helix-coil transition region of the same form as seen in trifluoroacetic acid/chloroform solutions. It is concluded that protonation of peptide groups is not essential, either for inducing the helix to coil transition itself or for observation of different and characteristic helix and coil αCH and NH shifts.     

Comparison of Hydrometallurgical Parameters of N,N‐Dialkylamides and of Tri‐n‐Butylphosphate

Straight‐chain N,N‐dihexyloctanamide (DHOA) and branched‐chain N,N‐di(2‐ethylhexyl)isobutyramide (D2EHIBA) have been identified as promising alternatives to tri‐n‐butylphosphate (TBP) for the reprocessing of spent uranium based fuels, and selective extraction of ²³³U from irradiated thorium fuels, respectively. The present work deals with the effects of different hydrodynamic parameters such as viscosity, density, and interfacial tension (IFT) on the phase‐separation time (PST) under uranium and thorium loading conditions. The IFT values have been determined under varying experimental conditions such as the aqueous nitric acid concentration, n‐dodecane purity, ligand concentration, and thorium/uranium loading conditions. These studies have suggested that the quality of n‐dodecane affects the IFT values of different solutions. The IFT values of D2EHIBA changed marginally (23.3 ± 0.9 mNm^?1) against THOREX feed solution for the wide range of D2EHIBA concentration (0.1–1.0 M). However, IFT, viscosity, and PST values increased with uranium loading of 1.1 M DHOA. These studies suggested that a lower phase‐disengagement rate with increased uranium loading was mainly due to the increased viscosity of the loaded 1.1 M DHOA solution.     

Extraction of Uranium from Seawater Using Magnetic Adsorbents

Abstract

A new process for the extraction of uranium from seawater was developed. In the process, uranium adsorption is effected using powdered magnetic adsorbents; the adsorbents are then separated from seawater using magnetic separation technology. This process is superior to a column method using a granulated hydrous titanium oxide adsorber bed in the following ways: (1) a higher rate of adsorption is realized because smaller particles are used in the uranium adsorption; and (2) blocking, which is inevitable in an adsorber bed, is eliminated.

The composite hydrous titanium-iron oxide as a magnetic adsorbent having high uranium adsorption capacity and magnetization can be prepared by adding urea to a mixed solution of titanium sulfate and ferrous sulfate. Adsorption and desorption of uranium and the removal of the adsorbent using a small-scale uranium extraction plant (about 15 m³/d) is reported, and the feasibility of uranium extraction from seawater by this process is demonstrated.     

Formation and characteristics of undoped and doped tetrahedral amorphous carbon films

Synthesis of undoped and doped tetrahedral amorphous carbon (ta-C) films has been achieved using magnetic field filtered plasma stream system in an ambient gas of pure Ar and Ar with N₂, respectively. The optical and electrical properties of these films as a function of the substrate bias voltages (V_b) or nitrogen partial pressures (P_N) have been studied using UV-visible optical absorption spectroscopy, Fourier-transform infra-red spectroscopy (FTIR) and measurements of electrical conductivity. The results show that ta-C films with a high sp³ fraction were formed when the V_b was in the range of −10 to −50 V. The optical band gap of such ta-C films was found to be larger than 3 eV. The incorporation of nitrogen into the ta-C films deposited at low P_N (P_N<25%), results in a slight drop in activation energy, which indicates that there is evidently some doping effect of nitrogen. The configurations of N atoms in ta-C network are identified and discussed.     

Synthesis and characterization of ion conducting cellulose esters with PEO side chains

Cellulose esters with poly(oxyethylene) (PEO) side chains, denoted COE-1 and HPCOE-1A, were prepared through the homogeneous reactions between cellulose or hydroxypropylcellulose and a PEO monocarboxylic acid in the presence of N,N′-dicyclohexylcarbodiimide and 4-N,N′-dimethylamino-pyridine. The LiCF₃SO₃ complexes of the two polymers were prepared, and the effects of salt concentration on the liquid crystallinity, ionic conductivity and morphology were investigated. It has been found that the two kinds of complexes are both thermotropic liquid crystalline materials and exhibit clearing temperatures, T_c, that increase with increasing salt concentration. The increase in T_c for each system is compensated approximately by a rise in T_g, leaving the liquid crystalline temperature ranges fairly constant. A non-Arrhenius temperature dependence of ionic conductivity is predominant in both systems with the maximum conductivities occurring at [Li]/[O]≈0.07. The environmental scanning electron microscopy reveals a very rough, array-like internal structure for the COE-1 complex at this salt concentration.     

Synthesis and photolytic properties of 1,5-di-N,N′-dialkylaminoanthraquinones containing acryloyl groups

Several l,5-di-N,N′-dialkyaminoanthraquinones containing acryloyl groups were synthesized and characterized by Fourier transform infrared (FTIR) and ¹H NMR spectroscopy. The photophysical and photoinduction properties of these anthraquinone derivatives were examined in solution, in combination with free radical producing agents such as hexa-aryl-bis-imidazoles (HABI). When UV–vis absorption and fluorescence spectroscopy were employed to investigate the photophysical process, results showed that the photobleaching rate of N-alkylaminoanthraquinones containing an acrylate group and HABI was much faster than the acrylate group-free N-alkylaminoanthraquinone/HABI combination. N-alkylaminoanthraquinone induced polymerization of 2-phenoxyethyl acrylate (POEA)/N-vinyl carbazole (NVC)/cellulose acetate butyrate (CAB) mixtures was studied using real-time infrared spectroscopy (RTIR). It was found that the rate of polymerization was faster if the acryloyl groups were connected to the N,N′-dialkylaminoanthraquinone structure and that 1,5-di-N,N′-dialkylaminoanthraquinone containing acryloyl groups was more sensitive to visible light system.     

Degree of crosslinking and mechanical properties of crosslinked poly(vinyl alcohol) beads for use in solid-phase organic synthesis

The limited swellability in polar media of the commonly used polystyrene/divinylbenzene (PS-DVB) support materials for solid-phase organic synthesis has led to the development of novel, highly swellable hydrophilic gels designed for use in aqueous or polar media. Poly(vinyl alcohol) beads crosslinked with epichlorohydrin (PVA-EP) were prepared by a two-step inverse-suspension polymerization method. While it is known that the morphology of the resulting beads can be controlled by the ratio of EP versus PVA as well as by the pre-crosslinking time, the actual degree of crosslinking of the beads and their mechanical properties remain unknown. It is therefore the purpose of this study to evaluate the actual degree of crosslinking of beads prepared with different quantities of crosslinker in the feed by spectroscopic (Raman, nuclear magnetic resonance) and chemical (functional group loading) methods. The mechanical properties of these swollen PVA-EP beads will be evaluated by single-bead unconfined compression in solvents such as water, N,N-dimethylformamide (DMF), and tetrahydrofuran (THF) and compared to model PS-DVB beads commonly used for solid phase synthesis.     

Expression of Cytochrome c3 from Desulfovibrio vulgaris in Plant Leaves Enhances Uranium Uptake and Tolerance of Tobacco

Cytochrome c3 (uranyl reductase) from Desulfovibrio vulgaris can reduce uranium in bacterial cells and in cell-free systems. This gene was introduced in tobacco under control of the RbcS promoter, and the resulting transgenic plants accumulated uranium when grown on a uranyl ion containing medium. The uptaken uranium was detected by EM in chloroplasts. In the presence of uranyl ions in sublethal concentration, the transgenic plants grew phenotypically normal while the control plants’ development was impaired. The data on uranium oxidation state in the transgenic plants and the possible uses of uranium hyperaccumulation by plants for environmental cleanup are discussed.     

Coordination nature of phase separation in oxide melts

The behavior of uranium oxide-silica, zirconia-alumina, zirconia-iron oxide, uranium oxideiron oxide, zirconia-alumina-iron oxide, and uranium oxide-iron oxide-zirconia melts was experimentally investigated in the air. The existence of two-phase fluids in these systems was confirmed. It is proposed that the reason for the phase separation is the formation of complexes with the general formula x[M³⁺O_8/2] [Me⁴⁺O_8/2]. The influence of a complex concentration on the density and surface tension of melts in the ZrO₂-Al₂O₃ system was demonstrated.     

Sensitivity Investigation of SW-B80N80 Nanotube to Polychlorinated Biphenyl-153 (PCB-153): DFT Methods

Polychlorinated biphenyls (PCBs) is one of the most persistent organic pollutants that exist in the atmosphere and can be concentrated in lithosphere and hydrosphere. Because of low biodegradability and lipophilicity, PCBs accumulate in fatty tissues and through oxidative stress could lead to cancers and central nervous system disorders. Currently, degradation of these synthetic pollutants is one of the environmental issues. The aim of this study is to provide a sensor for detection of PCB-153 (PCB-153). Nano boron nitride compounds (B_nN_m) are magic materials with high stability that can be used as a sensor for detection of chlorinated aromatic compounds. In this study, sensitivity of B₈₀N₈₀ as a form of single-walled boron nitride nanotubes (SW-B₈₀N₈₀ nanotube (8,8)) to PCB-153 has been investigated. The PCB-153 is closed to the SW-B₈₀N₈₀ nanotube and electron exchanges between them have been evaluated using density functional calculations by B3LYP/6–31G^* method. The calculation of the electronic properties has shown that SW-B₈₀N₈₀ nanotube is very sensitive to the presence of PCB-153 molecules. The HOMO/LUMO and gap energy (E_g) changes were considerable. Gap energy decreased from 4.214 eV to 2.022 eV during the formation of complex PCB-153-SW-B₈₀N₈₀ nanotube that leads to conversion of PCB-153 into the other products. According to thermodynamic parameter calculation through the IR-DFT method, it is expected that SW-B₈₀N₈₀ nanotube will be a suitable candidate in the elimination of PCB-153, as well as a gas sensor.     

F?rster Resonance Energy Transfer (FRET) as a Tool for Dissecting the Molecular Mechanisms for Maturation of the Shigella Type III Secretion Needle Tip Complex

Förster resonance energy transfer (FRET) provides a powerful tool for monitoring intermolecular interactions and a sensitive technique for studying Å-level protein conformational changes. One system that has particularly benefited from the sensitivity and diversity of FRET measurements is the maturation of the Shigella type III secretion apparatus (T3SA) needle tip complex. The Shigella T3SA delivers effector proteins into intestinal cells to promote bacterial invasion and spread. The T3SA is comprised of a basal body that spans the bacterial envelope and a needle with an exposed tip complex that matures in response to environmental stimuli. FRET measurements demonstrated bile salt binding by the nascent needle tip protein IpaD and also mapped resulting structural changes which led to the recruitment of the translocator IpaB. At the needle tip IpaB acts as a sensor for host cell contact but prior to secretion, it is stored as a heterodimeric complex with the chaperone IpgC. FRET analyses showed that chaperone binding to IpaB’s N-terminal domain causes a conformational change in the latter. These FRET analyses, with other biophysical methods, have been central to understanding T3SA maturation and will be highlighted, focusing on the details of the FRET measurements and the relevance to this particular system.     

Tetracarboxylic acid cobalt phthalocyanine SAM on gold: Potential applications as amperometric sensor for H2O2 and fabrication of glucose biosensor

This report describes the applications of cobalt tetracarboxylic acid phthalocyanine (CoTCAPc) self-assembled monolayer (SAM) immobilized onto a preformed 2-mercaptoethanol (Au-ME) SAM on gold surface (Au-ME-CoTCAPc SAM) as a potential amperometric sensor for the detection of hydrogen peroxide (H₂O₂) at neutral pH conditions. The Au-ME-CoTCAPc SAM sensor showed a very fast amperometric response time of approximately 1 s, good linearity at the studied concentration range of up to 5 μM with a coefficient R² = 0.993 and a detection limit of 0.4 μM oxidatively. Also reductively, the sensor exhibited a very fast amperometric response time (∼1 s), linearity up to 5 μM with a coefficient R² = 0.986 and a detection limit of 0.2 μM. The cobalt tetracarboxylic acid phthalocyanine self-assembled monolayer was then evaluated as a mediator for glucose oxidase (GOx)-based biosensor. The GOx (enzyme) was immobilized covalently onto Au-ME-CoTCAPc SAM using coupling agents: N-ethyl-N(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxy succinimide (NHS), and the results demonstrated a good catalytic behavior. Kinetic parameters associated with the enzymatic and mediator reactions were estimated using electrochemical versions of Lineweaver-Burk and Hanes equation, and the stability of the sensor was tested. The biosensor (Au-ME-CoTCAPc-GOx SAM) electrode showed good sensitivity (7.5 nA/mM) with a good detection limit of 8.4 μM at 3σ, smaller Michaelis-Menten constant (4.8 mM from Hanes plot) and very fast response time of approximately 5 s.     

Integration of multivariate SPM and FDD by parity space technique for a food pasteurization process

Multivariate statistical process monitoring (MSPM), contribution plots, and parity space fault diagnosis (FD) techniques are used to detect abnormal operation of dynamic processes and diagnose sensor and actuator faults. The methods are illustrated by monitoring the critical control points (CCP) and diagnosing causes of abnormal operation of a pilot pasteurization plant. An empirical model of the process is developed by using subspace state space system identification methods and normal process data. The process data collected under the influence of different magnitude and duration of faults in sensors and actuators are used to validate the MSPM and FD techniques. T² and squared prediction error (SPE_N) charts are used as MSPM charts. A parity space technique for dynamic stochastic systems and dynamic trends in contribution plots of T² and SPE_N statistics are used for FD. The detection and FD by these techniques show significant improvements over univariate methods.     

Studies on N-nitroso bile acid amides in relation to their possible role in gastrointestinal cancer

Cancers of the gastrointestinal tract account for a large proportion of neoplastic diseases which afflict humans. The etiology of gastrointestinal cancer has been attributed in part to exogenous carcinogens, such as food substances and environmental pollutants. Recent hypotheses suggest that carcinogens may arise endogenously. Evidence suggests that some bile acids and their isomeric metabolites may be involved in the pathogenesis of colon cancer. However, the mechanism responsible for their cancer-promoting effect is not clear. We and others propose that one mechanism for the mitogenic effects of bile acids may be N-nitrosation of their glycine and taurine amides; human gastric aspirates do contain small quantities of N-nitroso compounds of other substrates. Many foods contain nitrites and nitrates, which can react with bile acid amides to form N-nitroso derivatives. Our recent studies demonstrated the potential for N-nitroso conjugate formation from ursodeoxycholic acid, a 7β-epimer of chenodeoxycholic acid used as a drug Actigall^® to dissolve gallstones. The N-nitroso derivative of this compound, a direct-acting carcinogen, has a long half-life and, once nitrosated, is stable enough to survive passage through the gastrointestinal tract. We describe the synthesis of N-nitrosated derivatives of various bile acid conjugates and mechanisms of decomposition of (Z)- and (E)-bile acid diazoates. Studies of the effects of enzymes such as cholylglycine hydrolase on the N-nitroso bile acid conjugates and their reaction with DNA are also described. These studies may have important implications in the interplay of diet with endogenous substrates in the etiology of cancers of the stomach, liver, and colon.     

Controlled radical polymerization with polyolefin macroinitiator: a convenient and versatile approach to polyolefin-based block and graft copolymers

This paper introduces the new synthetic methodology of polyolefin-based block and graft copolymers with polar segments [e.g., polystyrene and poly(meth)acrylates]. Various brominated polyolefins were prepared by bromination of polyolefins with N-bromosuccinimide. The resulting brominated polyolefins were able to initiate the controlled radical polymerization of polar monomers, such as methyl methacrylate, ethyl acrylate, t-butyl acrylate, styrene and 2-(dimethylamino)ethyl acrylate, using a CuBr/N,N,N′,N″,N″-pentamethyldiethylenetriamine catalyst system, leading to a variety of polyolefin-based copolymers with a different content of the corresponding polar segment. Because of the accessible synthesis of polyolefin macroinitiators, this synthetic methodology is expected to result in the preparation of a wide range of polyolefin-based block and graft copolymers.