Irradiated oocysts in combination with inulin adjuvant-induced potent immune responses against Eimeria tenella infection in broiler chickens.

Coccidiosis is the leading parasitic disease in poultry. One of the most critical Eimeria species, Eimeria tenella, lives inside the cecal epithelial cells and induces bloody coccidiosis. The present study evaluated the effect of radiation-attenuated E. tenella oocytes mixed with inulin adjuvant on broiler chicken. Initially, the effect of irradiation on oocyst attenuation was confirmed. Then, one-day-old broilers (n = 90) were divided into nine groups on seven days of age as follow: Group 1 (400 attenuated oocysts + 1.00 mg of adjuvant), group 2 (400 attenuated oocysts + 0.50 mg adjuvant), group 3 (200 attenuated oocysts + 1.00 mg of adjuvant), group 4 (200 attenuated oocysts + 0.50 mg adjuvant), group 5 (1.00 mg adjuvant), group 6 (400 attenuated oocysts), group 7 (commercial vaccine), group 8 (negative control) and group 9 (blank). On day 21, we performed a challenge with E. tenella oocytes and investigated oocyst output and average weekly weight throughout the study. At the end of the study, we evaluated macroscopic lesion, histology, cytokine level and leukogram status. The results showed a statistically significant difference among groups. Furthermore, the optimal dose was 400 irradiated oocysts and 1.00 mg of inulin. Moreover, an X-ray could reduce the virulence of E. tenella oocytes. Inulin alone or combined with attenuated oocysts showed an acceptable effect on evaluated parameters.

In vitro cytotoxicity, antibacterial activity and HSA and ct-DNA interaction studies of chlorogenic acid loaded on γ-Fe2O3@SiO2 as new nanoparticles.

In this study, nanoparticles with both anticancer and antibacterial features were synthesized through loading chlorogenic acid (CGA) of essential oils on magnetic nanoparticles (MNPs). Characterization of γ-Fe2O3@SiO2-CGA MNPs was performed using Fourier transform infrared (FT-IR) spectroscopy and transmission electron microscopy (TEM) that show effective coating of the MNPs with SiO2 and CGA ligand and spherical shape of the nanoparticles with a mean diameter of 16 nm, respectively. The cytotoxicity study demonstrated that γ-Fe2O3@SiO2-CGA MNPs had fewer toxic effects on normal cells (Huvec) than on cancerous cells (U-87 MG, A-2780 and A-549), and could be a new potential candidate for use in biological and pharmaceutical applications. The interaction of calf thymus deoxyribonucleic acid (ct-DNA) with γ-Fe2O3@SiO2-CGA MNPs indicated that the anticancer activity might be associated with the DNA binding properties of γ-Fe2O3@SiO2-CGA MNPs. Moreover, the interaction of γ-Fe2O3@SiO2-CGA MNPs with human serum albumin (HSA) suggests that the native conformation of HSA was preserved at the level of secondary structure, indicating that the γ-Fe2O3@SiO2-CGA MNPs do not show any cytotoxicity effect when they are injected into the blood. Antibacterial tests were performed and represented γ-Fe2O3@SiO2-CGA MNPs attained better antibacterial function than CGA as free.

Synthesis of a targeted, dual pH and redox-responsive nanoscale coordination polymer theranostic against metastatic breast cancer in vitro and in vivo.

BACKGROUND: Nanoscale coordination polymers (nCP) have exhibited a great potential in designing of the theranostic platforms in the latest years. However, they have low selectivity for cancerous tissues and require to be modified for becoming effective cancer therapeutics. In this study, a novel nanoscale pH and redox-responsive coordination polymer with high selectivity was synthesized. METHODS: The nCP was synthesized by iron(III) chloride and dithiodiglycolic acid. After loading the prepared nCP with doxorubicin (DOX), nCP was coated with an amphiphilic copolymer composed of α-tocopheryl succinate-polyethylene glycol (VEP). Next, AS1411 aptamer was decorated on the VEP shell of the DOX-loaded nCP (Apt-VEP-nCP@DOX) to provide a guided drug delivery platform. RESULTS: The prepared platform demonstrated high DOX loading capacity and pH and redox-responsive DOX release. Apt-VEP-nCP@DOX displayed greater DOX internalization and toxicity toward breast cancer cells of 4T1 and MCF7 compared with that of non-targeted VEP-nCP@DOX. Also, the intravenous injection of Apt-VEP-nCP@DOX (a single dose) considerably suppressed the 4T1 tumor growth in vivo. Moreover, Apt-VEP-nCP@DOX showed outstanding magnetic resonance (MR) imaging capability for 4T1 adenocarcinoma diagnosis in ectopic 4T1 tumor model in mice. CONCLUSIONS: The developed innovative intelligent Apt-VEP-nCP@DOX could serve as a safe and biocompatible theranostic platform appropriate for further translational purposes against breast cancer.

Smart metal organic frameworks: focus on cancer treatment.

Metal-organic frameworks (MOFs), as a prominent category of hybrid porous materials constructed from metal clusters or ions with organic linkers, have been broadly employed as controlled systems of drug delivery due to their inherent interesting properties. These properties, such as high loading capability and tremendous biocompatibility, offer an exceptional opportunity for the treatment of cancer. In this review, we focus on the latest advancement of smart MOFs as systems of drug delivery for cancer treatment, diagnosis or both (theranostics). Furthermore, different methods and strategies for synthesizing smart MOFs with various mechanisms of drug release under diverse stimuli, such as pH, temperature, redox, magnetic field, enzyme, and light, were summarized and discussed. The current review helps in a better understanding of smart MOFs systems that would be useful for their smart design toward medical applications.

Spectroscopic studies on the interaction of aspartame with human serum albumin.

In this work the binding of artificial sweetener aspartame with human serum albumin (HSA) was studied at physiological pH. Binding studies of aspartame (APM) with HSA are useful to understand APM -HSA interaction, mechanism and providing guidance for the application and design of new and more efficient artificial sweeteners. The interaction was investigated by spectrophotometric, spectrofluorometric competition experiment and circular dichroism (CD) techniques. The results indicated that the binding of APM to HSA caused fluorescence quenching of HSA through static quenching mechanism with binding constant 1.42 × 10+4 M-1 at 298 K and the number of binding sites is approximately one. Thermodynamic parameters, enthalpy changes (ΔH) and entropy changes (ΔS) were calculated to be -41.20 kJ mol-1 and -58.19 J mol-1 K-1, respectively, according to van't Hoff equation, which indicated that reaction is enthalpically driven. Quenching of the fluorescence of HSA was found to be a static quenching process. The binding constants and number of binding sites were obtained at three different temperatures (298, 308 and 318 K). Combining above results and those of spectrofluorometric competition experiment and circular dichroism (CD), indicated that APM binds to HSA via Sudlow's site I. Furthermore, the study of molecular docking on HSA binding also indicated that APM can strongly bind to the site I (subdomain IIA) of HSA mainly by hydrophobic interaction and hydrogen bond interactions exist between APM and HSA.

Synthesis and spectroscopic characterization of new sulfanilamide-functionalized magnetic nanoparticles, and the usability for carbonic anhydrase purification: is there perspective for 'cancer treatment' application?

This investigation indicated an efficient procedure to purify human carbonic anhydrase II (hCA II) enzyme through sulfanilamide-functionalized (γ-Fe2O3-CPTES-SA) magnetic nanoparticles (MNPs), where synthesis of Fe3O4 MNPs was carried out using co-precipitation reaction. Next, 3-chloropropyltriethoxysilane (CPTES) was used to modify Fe3O4 nanoparticles and lastly, the surface of the nanoparticles was functionalized with sulfanilamide (SA) as a carbonic anhydrase ligand/inhibitor for binding to hCA II. The characterization of the synthesized nanoparticles was performed using various techniques. These characterization methods revealed that the MNPs were effectively coated with CPTES and SA, and the average diameter of the nanoparticles was approximately 21 nm. The possibility of interaction of γ-Fe2O3-CPTES-SA nanoparticles with hCA II was studied via multi-spectroscopic techniques. The protein isolated by this single-step procedure had high purity as confirmed by a single band on SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) which was also active after purification. By focusing on their drug loading capacity, and increasing their specificity and affinity to target CA-expressing cancer cells, the synthesized MNPs may dramatically impact the treatment of cancer and become suitable for clinical use in the near future.Communicated by Ramaswamy H. Sarma.

Experimental and molecular modeling studies on the DNA-binding of diazacyclam-based acrocyclic copper complex.

The interaction of a new macrocyclic copper complex, [CuL(NO3)2] in which L is 1,3,6,10,12,15-hexaaza tricyclo[13.3.1.16,10] eicosane was investigated in vitro under simulated physiological conditions by multi-spectroscopic techniques and molecular modeling study. The fluorescence spectroscopy and UV absorption spectroscopy indicated the complex interacted with ct-DNA in a groove binding mode while the binding constant of UV-vis and the number of binding sites were 1.0±0.2×104Lmol-1 and 1.01, respectively. The fluorometric studies showed that the reaction between the complex with ct-DNA is exothermic (ΔH=14.85kJmol-1; ΔS=109.54Jmol-1K-1). Circular dichroism spectroscopy (CD) was employed to measure the conformational change of DNA in the presence of [CuL(NO3)2] complex. Furthermore, the complex induces detectable changes in the viscosity of DNA. The molecular modeling results illustrated that the complex strongly binds to groove of DNA. Experimental and molecular modeling results showed that Cu(II) complex bound to DNA by a groove binding mode.

DNA-binding study of anticancer drug cytarabine by spectroscopic and molecular docking techniques.

The interaction of anticancer drug cytarabine with calf thymus DNA (CT-DNA) was investigated in vitro under simulated physiological conditions by multispectroscopic techniques and molecular modeling study. The fluorescence spectroscopy and UV absorption spectroscopy indicated drug interacted with CT-DNA in a groove-binding mode, while the binding constant of UV-vis and the number of binding sites were 4.0 ± 0.2 × 104 L mol-1 and 1.39, respectively. The fluorimetric studies showed that the reaction between the drugs with CT-DNA is exothermic. Circular dichroism spectroscopy was employed to measure the conformational change of DNA in the presence of cytarabine. Furthermore, the drug induces detectable changes in its viscosity for DNA interaction. The molecular modeling results illustrated that cytarabine strongly binds to groove of DNA by relative binding energy of docked structure -20.61 KJ mol-1. This combination of multiple spectroscopic techniques and molecular modeling methods can be widely used in the investigation on the interaction of small molecular pollutants and drugs with biomacromolecules for clarifying the molecular mechanism of toxicity or side effect in vivo.

Improving antiproliferative effect of the anticancer drug cytarabine on human promyelocytic leukemia cells by coating on Fe3O4@SiO2 nanoparticles.

In this study, Fe3O4@SiO2-cytarabine magnetic nanoparticles (MNPs) were prepared via chemical coprecipitation reaction and coating silica on the surface of Fe3O4 MNPs by Stöber method via sol-gel process. The surface of Fe3O4@SiO2 MNPs was modified by an anticancer drug, cytarabine. The structural properties of the samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Zetasizer analyzer, and transmission electron microscopy (TEM). The results indicated that the crystalline phase of iron oxide NPs was magnetite (Fe3O4) and the average sizes of Fe3O4@SiO2-cytarabine MNPs were about 23 nm. Also, the surface characterization of Fe3O4@SiO2-cytarabine MNPs by FT-IR showed that successful coating of Fe3O4 NPs with SiO2 and binding of cytarabine drug onto the surface of Fe3O4@SiO2 MNPs were through the hydroxyl groups of the drug. The in vitro cytotoxic activity of Fe3O4@SiO2-cytarabine MNPs was investigated against cancer cell line (HL60) in comparison with cytarabine using MTT colorimetric assay. The obtained results showed that the effect of Fe3O4@SiO2-cytarabine magnetic nanoparticles on the cell lines were about two orders of magnitude higher than that of cytarabine. Furthermore, in vitro DNA binding studies were investigated by UV-vis, circular dichroism, and fluorescence spectroscopy. The results for DNA binding illustrated that DNA aggregated on Fe3O4@SiO2-cytarabine MNPs via groove binding.

Experimental and molecular docking studies on DNA binding interaction of adefovir dipivoxil: advances toward treatment of hepatitis B virus infections.

The toxic interaction of adefovir dipivoxil with calf thymus DNA (CT-DNA) was investigated in vitro under simulated physiological conditions by multi-spectroscopic techniques and molecular modeling study. The fluorescence spectroscopy and UV absorption spectroscopy indicated drug interacted with CT-DNA in a groove binding mode. The binding constant of UV-visible and the number of binding sites were 3.33±0.2×10(4) L mol(-1)and 0.99, respectively. The fluorimetric studies showed that the reaction between the drug and CT-DNA is exothermic (ΔH=34.4 kJ mol(-1); ΔS=184.32 J mol(-1) K(-1)). Circular dichroism spectroscopy (CD) was employed to measure the conformational change of CT-DNA in the presence of adefovir dipivoxil, which verified the groove binding mode. Furthermore, the drug induces detectable changes in its viscosity. The molecular modeling results illustrated that adefovir strongly binds to groove of DNA by relative binding energy of docked structure -16.83 kJ mol(-1). This combination of multiple spectroscopic techniques and molecular modeling methods can be widely used in the investigation on the toxic interaction of small molecular pollutants and drugs with bio macromolecules, which contributes to clarify the molecular mechanism of toxicity or side effect in vivo.

DNA interaction studies of a novel Cu(II) complex as an intercalator containing curcumin and bathophenanthroline ligands.

A new copper(II) complex; [Cu(Cur)(DIP)](+2) in which Cur=curcumin and DIP=4,7-diphenyl-1,10-phenanthroline, was synthesized and characterized using different physico-chemical methods. Binding interaction of this complex with calf thymus (CT-DNA) has been investigated by emission, absorption, circular dichroism, viscosity, and differential pulse voltammetry and fluorescence techniques. The complex displays significant binding properties to the CT-DNA. In fluorimeteric studies, the binding mode of the complex with CT-DNA was investigated using methylene blue as a fluorescence probe. Fluorescence of methylene blue-DNA solution increased in the presence of increasing amounts of the complex. It was found that the complex is able to displace the methylene blue completely. This indicate intercalation of the complex between base pairs of DNA. The cleavage of plasmid DNA by the complex was also studied. We found that the copper(II) complex can cleave puC18 DNA. Furthermore, mentioned complex induces detectable changes in the CD spectrum of CT-DNA, a decrease in absorption spectrum, and an increase in its viscosity. All of the experimental results showed that the Cu(II) complex bound to DNA by an intercalative mode of binding.