CD44 Receptor-Mediated/Reactive Oxygen Species-Sensitive Delivery of Nanophotosensitizers against Cervical Cancer Cells

Stimulus-sensitive, nanomedicine-based photosensitizer delivery has an opportunity to target tumor tissues since oxidative stress and the expression of molecular proteins, such as CD44 receptors, are elevated in the tumor microenvironment. The aim of this study is to investigate the CD44 receptor- and reactive oxygen species (ROS)-sensitive delivery of nanophotosensitizers of chlorin e6 (Ce6)-conjugated hyaluronic acid (HA) against HeLa human cervical cancer cells. For the synthesis of nanophotosensitizers, thioketal diamine was conjugated with the carboxyl group in HA and then the amine end group of HA-thioketal amine conjugates was conjugated again with Ce6 (Abbreviated as HAthCe6). The HAthCe6 nanophotosensitizers were of small diameter, with sizes less than 200. Their morphology was round-shaped in the observations using a transmission electron microscope (TEM). The HAthCe6 nanophotosensitizers responded to oxidative stress-induced changes in size distribution when H₂O₂ was added to the nanophotosensitizer aqueous solution, i.e., their monomodal distribution pattern at 0 mM H₂O₂ was changed to dual- and/or multi-modal distribution patterns at higher concentrations of H₂O₂. Furthermore, the oxidative stress induced by the H₂O₂ addition contributed to the disintegration of HAthCe6 nanophotosensitizers in morphology, and this phenomenon accelerated the release rate of Ce6 from nanophotosensitizers. In a cell culture study using HeLa cells, nanophotosensitizers increased Ce6 uptake ratio, ROS generation and PDT efficacy compared to free Ce6. Since HA specifically bonds with the CD44 receptor of cancer cells, the pretreatment of free HA against HeLa cells decreased the Ce6 uptake ratio, ROS generation and PDT efficacy of HAthCe6 nanophotosensitizers. These results indicated that intracellular delivery of HAthCe6 nanophotosensitizers can be controlled by the CD44 receptor-mediated pathway. Furthermore, these phenomena induced CD44 receptor-controllable ROS generation and PDT efficacy by HAthCe6 nanophotosensitizers. During in vivo tumor imaging using HeLa cells, nanophotosensitizer administration showed that the fluorescence intensity of tumor tissues was relatively higher than that of other organs. When free HA was pretreated, the fluorescence intensity of tumor tissue was relatively lower than those of other organs, indicating that HAthCe6 nanophotosensitizers have CD44 receptor sensitivity and that they can be delivered by receptor-specific manner. We suggest that HAthCe6 nanophotosensitizers are promising candidates for PDT in cervical cancer.     

Development of a Novel Anti−CD44 Monoclonal Antibody for Multiple Applications against Esophageal Squamous Cell Carcinomas

CD44 is a cell surface glycoprotein, which is expressed on normal cells, and overexpressed on cancer cells. CD44 is involved in cell adhesion, migration, proliferation, survival, stemness, and chemo−resistance. Therefore, CD44 is thought to be a promising target for cancer diagnosis and therapy. In this study, we established anti−CD44 monoclonal antibodies (mAbs) by immunizing mice with a CD44 variant (CD44v3−10) ectodomain and screening using enzyme−linked immunosorbent assay. We then characterized them using flow cytometry, Western blotting, and immunohistochemistry. One of the established clones (C₄₄Mab−46; IgG₁, kappa) reacted with CD44 standard isoform (CD44s)−overexpressed Chinese hamster ovary−K1 cells (CHO/CD44s) or esophageal squamous cell carcinoma (ESCC) cell lines (KYSE70 and KYSE770). The apparent K_D of C₄₄Mab−46 for CHO/CD44s, KYSE70, and KYSE770 was 1.1 × 10⁻⁸ M, 4.9 × 10⁻⁸ M, and 4.1 × 10⁻⁸ M, respectively. C₄₄Mab−46 detected CD44s of CHO/CD44s and KYSE70, and CD44 variants of KYSE770 in Western blot analysis. Furthermore, C₄₄Mab−46 strongly stained the formalin−fixed paraffin−embedded ESCC tissues in immunohistochemistry. Collectively, C₄₄Mab−46 is very useful for detecting CD44 in various applications.     

Synthesis and caracterization of macromonomers of poly (2-methyl-2-oxazoline)-allyl by an acid exchanged clay as eco-catalyst

The different polymer networks were constructed by two kinds of associations, one is host-guest inclusion between P(AM/A-β-CD/NaA) and P(AM/BHAM/NaA), and the other is hydrophobic association of P(AM/BHAM/NaA). Under the high-speed shearing, the viscosity survival and recovery rate of different systems were investigated. The results show the inclusion complex (CD:BHAM = 2:1) has excellent shearing resistance performance, and it was also verified by dynamic light scattering (DLS). This is mainly because the strength of inclusive association is stronger than that of hydrophobic one. The conclusion was proved by time-temperature superposition as well. It shows that the activation energy E _a of the inclusion complex (CD:BHAM = 2:1), which represents the strength of association, has a maximum value, while the activation energy E _b of P(AM/BHAM/NaA) has also a maximum one because of the multiple associative sites of hydrophobic associations. The activation energy values of the inclusion complex (CD:BHAM = 1:1) are intermediate since there are two kinds of associations in this solution. This is exactly the reason that the complex (CD:BHAM = 1:1) has the best emulsifying property. Moreover, the conclusions related to emulsifying property have been verified by using a laser particle size analyzer and Turbiscan lab stability.     

H2O2-Responsive Organosilica-Doxorubicin Nanoparticles for Targeted Imaging and Killing of Cancer Cells Based on a Synthesized Silane-Borate Precursor

Doxorubicin (Dox) is a widely used fluorescent chemotherapy drug. Its primary delivery systems, based on physical adsorption to silica nanoparticles, can lead to low drug loading. Direct loading of Dox via covalent bonds during the formation of silica nanoparticles has never been reported. In this work, we designed and synthesized a silane-borate precursor, which contains not only an alkoxysilane moiety to form organosilica nanoparticles but also a phenylboronic acid moiety to react with diol-containing compounds. Using this compound, the covalent loading of Dox during the preparation of organosilica nanoparticles was effectively realized with a high drug loading content up to 22.4 %. Further modification by hyaluronic acid (HA) bestowed the Si-Dox@HA nanoparticles with the ability to target CD44-overexpressing cancer cells. The Si-Dox@HA nanoparticles exhibited H₂O₂-responsive release of about 80 % Dox and displayed seven-fold selectivity for killing cancer cells over normal cells, relative to Dox and Si-Dox nanoparticles. Moreover, these Si-Dox@HA nanoparticles are also suitable for targeted fluorescence imaging of CD44-overexpressing cancer cells.     

Dinitrophenol-Hyaluronan Conjugates as Multivalent Antibody-Recruiting Glycopolymers for Targeted Cancer Immunotherapy

Multivalent antibody-recruiting glycopolymers (MARGs) composed of hyaluronic acid (HA) grafted with multiple copies of dinitrophenol (DNP) were developed for targeted cancer immunotherapy. Structure-activity studies demonstrated that the MARGs were able to specifically recognize CD44-positive cancer cells and displayed remarkable antibody-recruiting capacities and tumor cell killing activities dependent on the introduced multivalent effect and the length of PEG linker. One of the MARGs, HA-[PEG₃-DNP]₈, showed the best capacity for clustering anti-DNP antibodies onto CD44-positive cancer cells and displayed potent in vitro anti-cancer activity by triggering complement dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Moreover, we found that HA-[PEG₃-DNP]₈ significantly inhibited the xenograft tumor growth of Babl/c nude mice bearing triple negative breast cancer cells, while it did not cause detectable histological cytotoxicity. Given the easy access of this type of natural glycopolymer and the practical synthesis approach, these MARGs provide promising immunotherapeutics for cancer immunotherapy.     

Theranostic Hyaluronic Acid–Iron Micellar Nanoparticles for Magnetic‐Field‐Enhanced in vivo Cancer Chemotherapy

The delivery of therapeutic cancer agents using nanomaterials has recently attracted much attention. Although encouraging progress with chemotherapeutics has been made, tumor treatment response remains unsatisfactory. To address this concern, we constructed a new micellar nanocomplex by covalently conjugating hyaluronic acid (HA) with an iron oxide nanoparticle (IONP). When an external magnetic field was applied to the tumor area, HA–IONP specifically accumulated in the tumor, due to the strong IONP magnetism. In addition, HA was shown to bind to cluster determinant 44 (CD44), which is overexpressed on tumor cells. With combined magnetic, CD44, and enhanced permeability retention (EPR) targeting, the efficient delivery of HA–IONP to the tumor is expected to enhance cancer treatment efficiency. After encapsulation of the chemotherapy drug homocamptothecin (HCPT), the theranostic potency of HA–IONP/HCPT (HIH) was investigated both in vitro and in vivo. The improved tumor homing behavior of HIH was observed by magnetic resonance imaging (MRI) when an external magnetic field was used. Moreover, HIH showed remarkable tumor ablation efficiency, with magnetic targeting after 3 mg kg^?1 intravenous administration (equivalent dose of free HCPT), and the tumors almost disappeared after treatment. No obvious systemic toxicity was detected. This excellent biocompatibility and tumor targetability suggests that HIH is a promising theranostic nanocomplex with great translational potency. Application of the HA–IONP platform could also be extended to delivery of other hydrophobic chemotherapy drugs or phototherapy agents.     

Nanoparticles Functionalised with Re(I) Tricarbonyl Complexes for Cancer Theranostics

Globally, cancer is the second (to cardiovascular diseases) leading cause of death. Regardless of various efforts (i.e., finance, research, and workforce) to advance novel cancer theranostics (diagnosis and therapy), there have been few successful attempts towards ongoing clinical treatment options as a result of the complications posed by cancerous tumors. In recent years, the application of magnetic nanomedicine as theranostic devices has garnered enormous attention in cancer treatment research. Magnetic nanoparticles (MNPs) are capable of tuning the magnetic field in their environment, which positively impacts theranostic applications in nanomedicine significantly. MNPs are utilized as contrasting agents for cancer diagnosis, molecular imaging, hyperfusion region visualization, and T cell-based radiotherapy because of their interesting features of small size, high reactive surface area, target ability to cells, and functionalization capability. Radiolabelling of NPs is a powerful diagnostic approach in nuclear medicine imaging and therapy. The use of luminescent radioactive rhenium(I), ^188/186Re, tricarbonyl complexes functionalised with magnetite Fe₃O₄ NPs in nanomedicine has improved the diagnosis and therapy of cancer tumors. This is because the combination of Re(I) with MNPs can improve low distribution and cell penetration into deeper tissues.     

Properties of hydroxyapatite/zirconium oxide nanocomposites

Effects of zirconium oxide (ZrO₂) nanoparticles additive on the microstructure and physical properties of hydroxyapatite (HA) were investigated. The HA powder was derived from natural bovine bone by a sequence of thermal processes. The composites containing nanoparticles of ZrO₂ (0.2–1.0 vol%) were fabricated by a solid-state reaction mixed oxide method. All samples showed traces of HA, beta-tricalcium phosphate (β-TCP) and alpha-tricalcium phosphate (α-TCP) phases while the x≥0.1 samples also showed ZrO₂ phase. Amount of β-TCP and α-TCP phases tend to decrease with ZrO₂. The additive inhibited grain growth as a result of a decrease in grain size. However, the x=0.2 sample exhibited higher hardness value which is consistent with the density data. In addition, bioactivity test suggested that the additive promoted an apatite forming with the values of Ca/P close to the value obtained from HA.     

Self-Assembled Polymeric Micelles Based on Hyaluronic Acid-g-Poly(d,l-lactide-co-glycolide) Copolymer for Tumor Targeting

Graft copolymer composed hyaluronic acid (HA) and poly(d,l-lactide-co-glycolide) (PLGA) (HAgLG) was synthesized for antitumor targeting via CD44 receptor of tumor cells. The carboxylic end of PLGA was conjugated with hexamethylenediamine (HMDA) to have amine end group in the end of chain (PLGA-amine). PLGA-amine was coupled with carboxylic acid of HA. Self-assembled polymeric micelles of HAgLG have spherical morphologies and their sizes were around 50–200 nm. Doxorubicin (DOX)-incorporated polymeric micelles were prepared by dialysis procedure. DOX was released over 4 days and its release rate was accelerated by the tumoric enzyme hyaluronidase. To assess targetability of polymeric micelles, CD44-positive HepG2 cells were employed treated with fluorescein isothiocyanate (FITC)-labeled polymeric micelles. HepG2 cells strongly expressed green fluorescence at the cell membrane and cytosol. However, internalization of polymeric micelles were significantly decreased when free HA was pretreated to block the CD44 receptor. Furthermore, the CD44-specific anticancer activity of HAgLG polymeric micelles was confirmed using CD44-negative CT26 cells and CD44-positive HepG2 cells. These results indicated that polymeric micelles of HaLG polymeric micelles have targetability against CD44 receptor of tumor cells. We suggest HAgLG polymeric micelles as a promising candidate for specific drug targeting.     

Antibacterial and magnetic response of site-specific cobalt incorporated hydroxyapatite

Hydroxyapatite [HA, Ca₁₀(PO₄)₆(OH)₂] based ceramics are a potential candidate for orthopedic implants, bone cements, and bioactive coating over metallic implants due to their compositional similarities [Ca/P = 1.67] with human bone. Cobalt doping in HA can greatly enhance angiogenesis and vascularization along with incorporating antimicrobial properties to HA. For the first time, this work reports the importance of Co doping sites on biological and magnetic properties of HA. In the current work, Co doing in HA has been carried out according to the chemical formula Ca₁₀(PO₄)₆Co_x(OH)_2-α and Ca_10-x Co_x(PO₄)₆(OH)₂, (x = 0, 0.2 and 0.3) to assess the correlation of individual Co incorporation sites on crystal chemistry, cytotoxicity, magnetic properties, ion leaching and antibacterial efficacy. Dependence of antibacterial efficacy on different doping sites revealed that cytocompatible Co doped HA is antibacterial against E. coli, and S. aureus mainly after substitution of Co in Ca site. Additionally, a minor antibacterial effect has been noticed after Co doping in OH channels. Interestingly, the Ca substituted Co doped HA shows Co leaching up to ∼758 ppb (obtained from inductively coupled plasma-mass spectrometry), which comes to only ∼27 ppb after incorporating Co in OH channel. This higher Co leaching (when doped at Ca site in comparison to that at OH channels) is the major cause of better antibacterial efficacy. Vibrating sample magnetometer measurements showed that the order of m_r and m_s values significantly changes after altering the doping sites, due to change in local Co environment. Thus, this work proves that different doping sites of Co doped HA can greatly enhance its antibacterial properties with significant changes in crystallographic and magnetic properties, which make Co doped HA an ideal choice as a bone replacement material or drug delivery agent with tailored properties depending on the doping sites.     

Characterization studies on plasma sprayed (AT/HA) bi-layered nano ceramics coating on biomedical commercially pure titanium dental implant

Hydroxyapatite (HA), Al₂O₃–13 wt%TiO₂ (AT) nanoparticles coated on bioactive commercially pure titanium (Cp-Ti) implant were fabricated by plasma spray coating technique. The fabricated monolayer AT, HA film of thickness 75 μm and bilayer (AT/HA) of thickness 150 μm and the coated film surface crystallinity, morphology and phases were investigated in terms of X-ray diffraction, SEM, FT-Raman spectroscopy. In this work, nanostructure AT, HA powders were plasma sprayed on the biomedical Cp-Ti implant surface improve corrosion resistance, and microhardness, surface roughness values compared to uncoated surface. Electrochemical corrosion test was carried out by simulated body fluid (SBF) with ionic concentrations comparable to that of human blood plasma and this result shows that improved corrosion resistance, for the bilayer (AT/HA) coated surface compared to a monolayer AT, HA coated surface. For Al₂O₃ addition with 13 wt%TiO₂ ceramics powder reinforced coating which can act as a barrier for the metal ion released from the implant surface. The in vitro analysis of the bilayer coated implant was good agreement with bone osteoinduction in the biological environment.     

Design,fabrication, and magnetic properties of novel (Ni,Cr,Zr)-co-doped M-type barium ferrite ceramics

Multicomponent co-doping is an effective method to balance the counteracting magnetic properties of ferrite ceramics. In this work, novel (Ni,Cr,Zr)-co-doped M-type barium hexaferrites (BaFe_12-3xNi_xCr_xZr_xO₁₉, x = 0–0.8) were designed and synthesized by traditional solid-state reaction. Thermogravimetric analysis indicated that NiO would participate in the formation of secondary phase NiFe₂O₄ in the as-synthesized powder. Through traditional solid-state sintering, by using the synthesized pure-phase magnetic powders, almost full-dense ceramics were fabricated. Visual high-temperature deformation analysis revealed that there was no obvious difference in the sintering behavior and densification temperature of the ceramics with different compositional x, due to the low sintering activity of the as-synthesized magnetic powders. And X-ray diffraction analysis indicated that all the fabricated ceramics are of pure-phase M-type barium ferrite, and the lattice parameter c/a firstly increased as x raised up to 0.4 and then remained almost unchanged with further increased x, even if the lattice distortion became heavier. Microstructure examination revealed that the grain size monotonously decreased as the quantity of the substituent ions increased. The remnant magnetization and coercivity of the fabricated ceramics decreased monotonously as x increased, while the saturated magnetization could be maintained till the samples with x ≤ 0.4. Taking all the parameters into consideration, the samples with x = 0.4 might be a good candidate for transformer cores.     

Solubility and diffusivity of CO2 in poly(l-lactide)-hydroxyapatite and poly(d,l-lactide-co-glycolide)-hydroxyapatite composite biomaterials

Solubility and diffusivity of supercritical CO₂ in poly(l-lactide)-hydroxyapatite (PLLA-HA) and poly(d,l-lactide-co-glycolide)-hydroxyapatite (PLGA-HA) composite materials were measured using a magnetic suspension balance at a temperature of 313 K and a pressures range of 10-30 MPa. The effect of the HA concentration on the solubility and diffusivity was investigated by varying filler content in the range of 0-50 wt%. For the PLLA-HA composites the solubility decreases with the increase of filler concentration. Diffusivity of the gas in the substrate is also lower as the HA content increases. In the case of PLGA-HA composites, small filler content favors the solubility and diffusivity of CO₂ due to incomplete wetting of the solid particles by the polymer. As the amount of HA increases solubility decreases. The results suggest that dense CO₂ could be used as a ‘green’ processing agent for composite biomaterials when organic solvents or high temperatures should be avoided.     

Expression and Significance of CD44, CD47 and c-met in Ovarian Clear Cell Carcinoma

Aims: The aim of the present study is to investigate the differential expression of CD44, CD47 and c-met in ovarian clear cell carcinoma (OCCC), the correlation in their expression and their relationship with the biological behavior of OCCC. Methods: We used immunohistochemistry to examine the expression of CD44, CD47 and c-met in OCCC (86 cases) and investigated the effects of the expression and interaction of these molecules on the development of OCCC. Results: CD44, CD47 and c-met expression was significantly high in OCCC. Expression of CD44 and CD47 correlated with patient surgical stage, chemotherapy resistance and prognosis (all p < 0.05), and expression of c-met correlated with chemotherapy resistance and prognosis (all p < 0.05), but did not correlate with lymph node metastasis (all p > 0.05). The surgical stage, CD44, CD47 and c-met expression were independent risk factors for OCCC prognosis (all p < 0.05). Patients with low levels of CD44, CD47 and c-met showed better survival than those with high levels (all p < 0.05). There was a positive correlation between CD44 (or CD47) and c-met, as well as between CD44 and CD47 (the Spearman correlation coefficient r_s was 0.783, 0.776 and 0.835, respectively, all p < 0.01). Additionally, pairwise correlation analysis of these three markers shows that the high expression of CD44/CD47, CD44/c-met and CD47/c-met were correlated with patient surgical stage, chemotherapy resistance and prognosis (all p < 0.05), but did not correlate with lymph node metastasis (all p > 0.05). Conclusions: Expression of CD44, CD47 and c-met was upregulated in OCCC and pairwise correlation. CD44, CD47 and c-met may have synergistic effects on the development of OCCC and are prognostic factors for ovarian cancer.     

Optimized Anti-pathogenic Agents Based on Core/Shell Nanostructures and 2-((4-Ethylphenoxy)ethyl)-N-(substituted-phenylcarbamothioyl)-benzamides

The purpose of this study was to design a new nanosystem for catheter surface functionalization with an improved resistance to Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853 colonization and subsequent biofilm development. New 2-((4-ethylphenoxy)methyl)-N-(substituted-phenylcarbamothioyl)-benzamides were synthesized and used for coating a core/shell nanostructure. Their chemical structures were elucidated by NMR, IR and elemental analysis, being in agreement with the proposed ones. Fe₃O₄/C₁₂ of up to 5 nm size had been synthesized with lauric acid as a coating agent and characterized by XRD, FT-IR, TGA, TEM and biological assays. The catheter pieces were coated with the fabricated nanofluid in magnetic field. The microbial adherence ability was investigated in 6 multiwell plates by using culture based methods and Scanning Electron Microscopy (SEM). The nanoparticles coated with the obtained compounds 1a–c inhibited the adherence and biofilm development ability of the S. aureus and P. aeruginosa tested strains on the catheter functionalized surface, as shown by the reduction of viable cell counts and SEM examination of the biofilm architecture. Using the novel core/shell/adsorption-shell to inhibit the microbial adherence could be of a great interest for the biomedical field, opening new directions for the design of film-coated surfaces with improved anti-biofilm properties.     

Beta-sialon phosphor deposits fabricated by electrophoretic deposition (EPD) process in a magnetic field

Phosphor deposits of β-sialon:Eu²⁺ were prepared by electrophoretic deposition (EPD) process within a magnetic field. Under the action of the magnetic force, which was parallel to the direction of the electric field of the EPD, the β-sialon:Eu²⁺ crystals were aligned along the c-axis of the hexagonal cell unit to form an oriented deposit via the EPD fabrication. Higher orientation degree was obtained at longer depositing time (300 s) and stronger applied magnetic field (12 T). The oriented deposit aligned along the c-axis obtained higher relative deposit density than the randomly fabricated deposit. Due to the improved relative density, the oriented deposit prepared within the magnetic field possessed an enhanced external quantum efficiency (η_ex). Also, because of different relative densities of the deposits prepared within and without the magnetic field, they presented different chromaticity coordinates.     

Critical role of the conformation of comonomer units in isomorphic crystallization of poly(hexamethylene adipate-co-butylene adipate) forming Poly(hexamethylene adipate) type crystal

The isothermal crystallization of isomorphic Poly(hexamethylene adipate-co-butylene adipate) [P(HA-co-BA)], with the HA unit content ranged from 100 to 45 mol%, forming the Poly(hexamethylene adipate) [PHA] type crystal was investigated with DSC, FTIR and WAXD. The BA units were found adopting their all-trans conformation in the crystalline phase of PHA type crystal. The inclusion of the BA units into the PHA type crystal was highly preferred in the isothermal crystallization at 25 °C. The exclusion of the BA units from the crystalline phase of the PHA type crystal was enhanced by elevating the crystallization temperature (T_c), depending on the content of comonomer units. Increasing the HA unit content enhances the formation of the all-trans conformation of the BA units in the PHA type crystal. At low T_c, such an enhancement significantly helps in retarding the exclusion of the BA units from the PHA type crystalline lattice. On the other hand, at high T_c, the difficulty for forming the stable all-trans conformation of the BA units in cocrystal increased and hence the exclusion of the BA units from the cocrystal was accelerated. In conclusion, the all-trans conformation of the BA units can also play a critical role in the isomorphic crystallization of the P(HA-co-BA)s forming the PHA type crystal.     

Ortho Isomeric Mn(III) N-Alkyl- and Alkoxyalkylpyridylporphyrins—Enhancers of Hyaluronan Degradation Induced by Ascorbate and Cupric Ions

High levels of hyaluronic acid (HA) in tumors correlate with poor outcomes with several types of cancers due to HA-driven support of adhesion, migration and proliferation of cells. In this study we explored how to enhance the degradation of HA into low-molecular fragments, which cannot prevent the immune system to fight tumor proliferation and metastases. The physiological solution of HA was exposed to oxidative degradation by ascorbate and cupric ions in the presence of either one of three ortho isomeric Mn(III) substituted N-alkyl- and alkoxyalkylpyridylporphyrins or para isomeric Mn(III) N-methylpyridyl analog, commonly known as mimics of superoxide dismutase. The changes in hyaluronan degradation kinetics by four Mn(III) porphyrins were monitored by measuring the alteration in the dynamic viscosity of the HA solution. The ortho compounds MnTE-2-PyP⁵⁺ (BMX-010, AEOL10113), MnTnBuOE-2-PyP⁵⁺ (BMX-001) and MnTnHex-2-PyP⁵⁺ are able to redox cycle with ascorbate whereby producing H₂O₂ which is subsequently coupled with Cu(I) to produce the ^•OH radical essential for HA degradation. Conversely, with the para analog, MnTM-4-PyP⁵⁺, no catalysis of HA degradation was demonstrated, due to its inertness towards redox cycling with ascorbate. The impact of different Mn(III)-porphyrins on the HA decay was further clarified by electron paramagnetic resonance spectrometry. The ability to catalyze the degradation of HA in a biological milieu, in the presence of cupric ions and ascorbate under the conditions of high tumor oxidative stress provides further insight into the anticancer potential of redox-active ortho isomeric Mn(III) porphyrins.     

Magneto-dielectric laminated Ba(Fe0.5Nb0.5)O3-Bi0.2Y2.8Fe5O12 composites with high dielectric constant and high permeability

Magneto-dielectric laminated ceramic composites of xBa(Fe_0.5Nb_0.5)O₃-(1-x)Bi_0.2Y_2.8Fe₅O₁₂(BFN-BYIG) with high volume fractions of the giant dielectric constant material BFN (x=10, 30, 50, 70 wt%) were fabricated by the solid-state sintering method. Microstructure, dielectric and magnetic properties of the composites were investigated. The composites possess stable dielectric properties in the frequency range from 100 Hz to 1 MHz with high dielectric constant and low dielectric loss. The maximum permeability of the magneto-dielectric laminated composites reaches up to about 25. And the magnetic behaviors are strongly dependent on the mass ratio of BYIG. The results indicate that such multilayer structures of BFN/BYIG can enhance the permeability and decrease the dielectric and magnetic loss efficiently.     

La1−xCaxMnO3:Ag0.2 (0.25 ≤ x ≤ 0.31) ceramics with high temperature coefficient of resistivity under magnetic field

The polycrystalline La_1?xCa_xMnO₃ ceramics exhibit good electromagnetic performance, i.e., high temperature coefficient of resistivity (TCR), which can be tuned flexibly with respect to structures. Unfortunately, the magnetic field applied to these materials causes a massive decrease in TCR, which hinders their practical applications. In this study, polycrystalline ceramic La_1?xCa_xMnO₃:Ag_0.2 was fabricated by sol–gel and solid–phase doping methods, and subsequently vast TCR was obtained in the magnetic field for ceramic with x = 0.2. For this polycrystalline material, high value of TCR (58.65%·K^?1, 62.00%·K^?1) could be maintained with or without magnetic field with metal–insulator (M ? I) transition temperature near room temperature range. Extremely high value of TCR in the presence of magnetic field is attributed to the spin–spin coupling effect, which is beneficial to the sensitivity of M ? I transition, generating vast TCR in the magnetic field. Overall, these findings provide new prospects for future applications in infrared bolometers.