Molecular Insights into the Binding and Conformational Changes of Hepcidin25 Blood Peptide with 4-Aminoantipyrine and Their Sorption Mechanism by Carboxylic-Functionalized Multiwalled Carbon Nanotubes: A Comprehensive Spectral Analysis and Molecular Dynamics Simulation Study.

In this work, the main purpose is to analyze and understand the mechanism and thermodynamic interactions of carboxylic acid-functionalized multiwalled carbon nanotubes (cf-MWCNTs) and 4-aminoantipyrine (AAP) with human hepcidine25 (Hep25) using multispectroscopic and molecular docking modeling methods, binding free energy calculations, and molecular dynamics (MD) simulations under physiological conditions. AAP belongs to a class of persistent environmental contaminants, and its residue is a potential hazard to human health, exhibiting a high binding affinity with blood peptides. Hepcidin is a 25-residue peptide hormone with four disulfide bonds that regulates the iron balance in vertebrates and contributes to host immunity as a cysteine-rich antimicrobial peptide. Due to their diverse properties and pollutant absorption capabilities, CNTs demonstrate important biological effects in biological applications, particularly in the noncovalent interactions with blood peptides. A comprehensive molecular dynamics simulation integrated with molecular docking methodologies was employed to explore the binding free energy between AAP and Hep25, identify binding sites, elucidate thermodynamic characteristics, and evaluate the binding forces governing their interaction. The investigation delved into elucidating the precise binding site of AAP within the Hep25 protein and thoroughly analyzed the impact of AAP on the microenvironment and conformational dynamics of Hep25. The circular dichroism (CD) experimental results highlight a reduction in ß-sheet composition following the introduction of AAP and cf-MWCNT. In addition, outcomes from fluorescence spectroscopy demonstrate that both cf-MWCNT and AAP significantly attenuated Hep-25 fluorescence via a static quenching mechanism. According to the MD simulations, the presence of AAP induces changes in the secondary structure of Hep25 and enhances its hydrophobicity. Additionally, our findings demonstrated that alongside the alteration in protein structure and functionality induced by contaminants, cf-MWCNTs possess the capability to mitigate the contaminant-induced effects on Hep25 activity while preserving the overarching structural integrity of Hep25. Based on the distance and RDF data, we found that during the simulation the presence of the cf-MWCNT causes the AAP to move away from the Hep25, and as a result fewer and weaker interactions of the AAP with the Hep25 will be observed. Likewise, free energy calculations indicate that the binding of Hep25 to AAP and cf-MWCNT involves electrostatic, π-cationic, and π-π stacking interactions. The research findings offer invaluable insights into the intricate influence of pollutants and carbon nanotubes on protein functionality within the circulatory system and their toxicity in vivo for prospective investigations.

Ultrasensitive Aptasensing Platform for the Detection of ß-Amyloid-42 Peptide Based on MOF Containing Bimetallic Porphyrin Graphene Oxide and Gold Nanoparticles.

The prompt detection of diseases hinges on the accessibility and the capability to identify relevant biomarkers. The integration of aptamers and the incorporation of nanomaterials into signal transducers have not only expedited but also enhanced the development of nanoaptasensors, enabling heightened sensitivity and selectivity. Here, the bimetallic nickel-cobalt-porphyrin metal-organic framework ((Ni + Cu)TPyP MOF) is regarded as an electron mediator, immobilization platform for an Alzheimer aptamer and to increase the electrochemical signal for the detection of the main biomarker of Alzheimer's disease (AD), amyloid ß (Aß-42). Furthermore, the ((Ni + Cu)TPyP MOF) was combined with reduced graphene oxide (rGO) and gold nanoparticles (AuNPs), on a gold electrode (GE) to provide an efficient interface for immobilizing aptamer strands. Concurrently, the incorporation of rGO and AuNPs imparts enhanced electrical conductivity and efficacious catalytic activity, establishing them as adept electrochemical indicators. Owing to the superior excellent electrical conductivity of rGO and AuNPs, coupled with the presence of ample mesoporous channels and numerous Ni and Cu metal sites within (Ni + Cu)TPyP MOF, this nanostructure with abundant functional groups is proficient in immobilizing a substantial quantity of aptamer. These interactions are achieved through robust π-π stacking and electrostatic interactions, alongside the high affinity between the thiol group of the aptamer and AuNPs concurrently. The as-prepared ternary (Au@(Ni + Cu)TPyP MOF/rGO) nanostructure electrode exhibited an enhancement in its electrochemically active surface area of about 7 times, compared with the bare electrode and the Aß-42 redox process is highly accelerated, so the peak currents are significantly higher than those obtained with bare GE substrate. Under the optimized conditions, the designed aptasensor had the quantitative detection of Aß-42 with a low detection limit of 48.6 fg mL-1 within the linear range of 0.05 pg mL-1 to 5 ng mL-1 by differential pulse voltammetry (DPV), accompanied by precise reproducibility, satisfactory stability (95.6% of the initial activity after 10 days), and minimal impact of interfering agents. Recorded results in human blood plasma demonstrated the high efficacy of porphyrin MOF system sensing even in the clinical matrix. The great performance of this aptasensor indicates that our new design of Au@(Ni + Cu)TPyP MOF/rGO nanostructure provides more opportunities for the detection of chemical signals in early diagnosis of Alzheimer's disease.

Design and characterization of a novel pH-sensitive biocompatible and multifunctional nanocarrier for in vitro paclitaxel release.

Breast cancer is one of the main reasons of women's mortality. A novel ternary combination of ZnAl-layered double hydroxides (LDH), cobalt ferrite (CoFe2O4) and N-graphene quantum dots (N-GQDs) proposes a pH-sensitive multifunctional nanocomposite that can improve therapeutic features of each compound; this is a notable strategy to make biocompatible materials with unique properties for paclitaxel (PTX) delivery in breast cancer cells. For proving the surface modification process of materials, electrochemical techniques including cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were carried out. By coating PEG on the surface of the N-GQDs/CoFe2O4/LDH, it developed a drug delivery system with low toxicity, an excellent encapsulation efficiency 88.4%, drug loading capacity of ca. 31%, and slow and sustained release behavior (9% after 72 h) under normal physiological conditions. Besides, a high drug release (~69%) at low-pH as a model of the extracellular tumor environment indicated a pH-sensitive release behavior. Moreover, cell viability assay proved the negligible cytotoxicity on normal cells (L929) and the improved growth inhibition effect of PTX/N-GQDs/CoFe2O4/LDH nanocarrier on MCF7 cancer cells. Blood compatibility test values with respect to red blood cell aggregation (RBC), coagulation prothrombin time (PT), activated partial thromboplastin time (APTT), and complement activation (C3 and C4 levels) remained within normal ranges without toxicity effect on RBCs and complement factors. Overall, this novel designed PTX/N-GQDs/CoFe2O4/LDH nanocarrier with tremendously biocompatible, slow-release and pH-dependent features could be considered as a theranostic candidate for various anticancer drugs delivery and cancer therapy.

A high-sensitive electrochemical DNA biosensor based on a novel ZnAl/layered double hydroxide modified cobalt ferrite-graphene oxide nanocomposite electrophoretically deposited onto FTO substrate for electroanalytical studies of etoposide.

The combination of layered double hydroxides (LDHs), cobalt ferrite (CoFe2O4) and graphene oxide (GO) creates a ternary nanocomposite that can incredibly improve advantages of each compound; this is an impressive way to attain multifunctional materials with attractive properties. In this study, a new high-sensitive electrochemical DNA biosensor was fabricated for the electroanalytical studies of etoposide using a novel ZnAl/layered double hydroxide modified cobalt ferrite-graphene oxide nanocomposite (GO/CoFe2O4/ZnAl-LDH) that was electrophoretically deposited (EPD) on the fluorine tin oxide (FTO) substrate. This DNA biosensor was prepared via electrostatic adsorption of DNA onto the GO/CoFe2O4/ZnAl-LDH/FTO electrode. The electrochemical behavior of electrodes was characterized using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). EIS plot obviously demonstrated a rapid electron transport at low frequencies for GO/CoFe2O4/ZnAl-LDH. Differential pulse voltammetry (DPV) and square wave anodic stripping voltammetry (SWASV) were employed for the electrochemical detection of ETO. The results revealed that DNA/GO/CoFe2O4/ZnAl-LDH/FTO bioelectrode had ultrahigh sensitivity to ETO with the detection limit of 0.0010 µM in the linear range of 0.2-10 µM. In addition, the developed biosensor revealed precise reproducibility and excellent stability of about 95% of the initial activity after 6-7 weeks. On the other hand, the present bioelectrode was also capable of discriminating different interferences and was also used to detect etoposide in real samples such as human blood plasma, serum and urine with good recoveries, ranging from 97.0% to 104.0%. The obtained results of the excellent performance of this biosensor could be assigned to the active reaction sites and good electrochemical activity of nanocomposites, hence helping increase the DNA immobilization and accelerate the electron transfer more effectively on the surface electrode.