Characterization and Evaluation of Nano-niosomes Encapsulating Docetaxel against Human Breast, Pancreatic, and Pulmonary Adenocarcinoma Cancer Cell Lines.

Background: Docetaxel (DXL) is an antineoplastic agent for cancer treatment, the therapeutic efficiency of which is limited due to low solubility, hydrophobicity, and tissue specificity. Objective: In this study, nano-niosomes were introduced for improving therapeutic index of DXL. Material and Methods: In this experimental study, two nano-niosomes were synthesized using Span 20® and Span 80® and a thin film hydration method with DXL loading (DXL-Span20 and DXL-Span80). Characterization, in-vitro cytotoxicity and bioavailability of the nano-niosomes was also evaluated via in-vivo experiments. Results: DXL-Span20 and DXL-Span80 have vesicles size in a range of 84-90 nm and negative zeta potentials. DXL entrapment efficiencies were obtained as 69.6 and 74.0% for DXL-Span20 and DXL-Span80, respectively; with an in-vitro sustained release patterns. Cytotoxicity assays were performed against MDA-MB-231, Calu-6, and AsPC-1 cell lines, and the results indicated that DXL loading into nano-niosomes led to decrement in values of half-maximal inhibitory concentration (IC50) at least 2.5 times and at most 6.5 times, compared to free DXL. Moreover, the rat blood bioavailability of DXL after intraperitoneal administration and the pharmacokinetic parameters indicated higher DXL plasma level and the higher effectiveness of DXL-Span80 compared to DXL-Span20. Conclusion: Carrying DXL by the nano-niosomes led to enhanced cytotoxicity (and lower IC50 values) and higher efficacy with enhanced pharmacokinetic parameters.

Synchronized Chemotherapy/Photothermal Therapy/Sonodynamic Therapy of Human Triple-Negative and Estrogen Receptor-Positive Breast Cancer Cells Using a Doxorubicin-Gold Nanoclusters-Albumin Nanobioconjugate.

OBJECTIVE: Novel strategies for treating triple-negative breast cancer (TNBC) are ongoing because of the lack of standard-of-care treatment. Nanoframed materials with a protein pillar are considered a valuable tool for designing multigoals of energy-absorbing/medication cargo and are a bridge to cross-conventional treatment strategies. METHODS: Nanobioconjugates of gold nanoclusters-bovine serum albumin (AuNCs-BSA) and doxorubicin-AuNCs-BSA (Dox-AuNCs-BSA) were prepared and employed as a simultaneous double photosensitizer/sonosensitizer and triple chemotherapeutic/photosensitizer/sonosensitizer, respectively. RESULTS: The highly stable AuNCs-BSA and Dox-AuNCs-BSA have ζ potentials of -29 and -18 mV, respectively, and represent valuable photothermal and sonodynamic activities for the combination of photothermal therapy and sonodynamic therapy (PTT/SDT) and synchronized chemotherapy/photothermal therapy/sonodynamic therapy (CTX/PTT/SDT) of human TNBC cells, respectively. The efficiency of photothermal conversion of AuNCs-BSA was calculated to be a promising value of 32.9%. AuNCs-BSA and Dox-AuNCs-BSA were activated on either laser light irradiation or ultrasound exposure with the highest efficiency on the combination of both types of radiation. CTX/PTT/SDT of MCF-7 and MDA-MB-231 breast cancer cell lines by Dox-AuNCs-BSA were evaluated with the MTT cell proliferation assay and found to progress synergistically. CONCLUSION: Results of the MTT assay, detection of the generation of intracellular reactive oxygen species and occurrence of apoptosis in the cells confirmed that CTX/PTT/SDT by Dox-AuNCs-BSA was attained with lower needed doses of the drug and improved tumor cell ablation, which would result in the enhancement of therapeutic efficacy and overcoming of therapeutic resistance.

Immunological mechanisms of the nucleocapsid protein in COVID-19.

The emergence of corona virus disease 2019 (COVID-19), resulting from Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has left an indelible mark on a global scale, causing countless infections and fatalities. This investigation delves into the role of the SARS-CoV-2 nucleocapsid (N) protein within the HEK293 cells, shedding light on its influence over apoptosis, interferon signaling, and cytokines production. The N gene was amplified, inserted into the pAdTrack-CMV vector, and then transfected to the HEK293 cells. Changes in the expression of IRF3, IRF7, IFN-ß, BAK, BAX, and BCL-2 genes were evaluated. The levels of proinflammatory cytokines of IL-6, IL-12, IL-1ß, and TNF-α were also determined. The N protein exhibited an anti-apoptotic effect by modulating critical genes associated with apoptosis, including BAK, BAX, and BCL-2. This effect potentially prolonged the survival of infected cells. The N protein also played a role in immune evasion by suppressing the interferon pathway, evidenced by the downregulation of essential interferon regulatory factors of IRF3 and IRF7, and IFN-ß expression. The N protein expression led to a substantial increase in the production of proinflammatory cytokines of IL-6, IL-12, IL-1ß, and TNF-α. The N protein emerged as a versatile factor and was exerted over apoptosis, interferon signaling, and cytokine production. These findings carry potential implications for the development of targeted therapies to combat COVID-19 and mitigate its global health impact.

Synthesis of Flower-like Nickel Hydroxide Nanosheets and Application in Electrochemical Determination of Famotidine.

An electrochemical sensor was designed and fabricated for electrocatalytic oxidation and determination of famotidine in pharmaceutical forms. The electrochemical oxidation process and its kinetics were investigated using cyclic voltammetry, steady-state polarization measurements, and chronoamperometry techniques, and also the analytical measurements were performed by amperometry. Upon addition of the drug into the solution, cyclic voltammograms of the fabricated sensor exhibited an increased anodic peak current associated with a decrease in the corresponding cathodic current. These results suggested an electrocatalytic EC' oxidation mechanism for famotidine on the oxyhydroxide species immobilized on the electrode surface. Accordingly, a mechanism involving generation of Ni3+ active sites and their subsequent consumption by the drug was proposed. Moreover, the corresponding rate law under the control of charge transfer was developed and kinetic parameters were derived. A sensitive and time-saving amperometric procedure was also developed for the analysis of famotidine with a detection limit of 5.91 mmol L-1. Using the developed amperometric procedure, famotidine was successfully analyzed in the presence of ibuprofen. The developed sensor in this study displayed enhanced sensitivity and selectivity, compared to some other reported methods.

A nanoemulsion-based delivery system for imatinib and in vitro anticancer efficacy

A self-nanoemulsifying drug delivery system (SNEDDS) composed of ethyl oleate, Tween 80 and polyethylene glycol 600 was prepared as a new route to improve the efficacy of imatinib. The drug-loaded SNEDDS formed nanodroplets of ethyl oleate stabilized by Tween 80 and polyethylene glycol 600 with a diameter of 81.0±9.5 nm. The nanoemulsion-based delivery system was stable for at least two months, with entrapment efficiency and loading capacity of 16.4±0.1 and 48.3±0.2%, respectively. Imatinib-loaded SNEDDS was evaluated for the drug release profiles, and its effectiveness against MCF-7 cell line was investigated. IC50 values for the imatinib-loaded SNEDDS and an imatinib aqueous solution were 3.1 and 6.5 µg mL-1, respectively.

An electrochemical peptide-based biosensor for the Alzheimer biomarker amyloid-ß(1-42) using a microporous gold nanostructure.

Alzheimer's disease (AD) is connected to aggregation of amyloid-ß (Aß) peptide and formation of insoluble plaques in the brain. Aß level can be monitored as an AD early diagnosis route. In this study, an irregular shaped microporous gold nanostructure with a typical size of 150 × 250 nm was electrodeposited on a polycrystalline gold surface at 0 mV (vs. AgCl) using sodium alendronate. The nanostructure was then characterized by field-emission scanning electron microscopy. An electrochemical peptide-based biosensor was fabricated by immobilizing an Aß(1-42)-binding peptide on the gold nanostructure. Binding of Aß(1-42) by the peptide was followed electrochemically using ferro/ferricyanide as a redox probe. Differential pulse voltammograms in a potential range of 0-500 mV (vs. AgCl) with typical peak potentials at 224 mV are linear in the 3-7000 pg mL-1 Aß(1-42) concentration range, with a 0.2 pg mL-1 detection limit. The biosensor is free of interferences and was applied to the quantitation of Aß(1-42) in artificial cerebrospinal fluid and spiked serum samples. Graphical abstractSchematic presentation of an immobilized amyloid-ß(1-42)-specific peptide on the surface of a microporous gold nanostructure to fabricate an electrochemical biosensor for early diagnosis of Alzheimer's disease. Aß(1-42) capturing by the peptide led to repulsion of ferrocyanide/ferricyanide redox couple.

Applications of Nanoflowers in Biomedicine.

BACKGROUND: Nanotechnology has opened new windows for biomedical researches and treatment of diseases. Nanostructures with flower-like shapes (nanoflowers) which have exclusive morphology and properties have been interesting for many researchers. METHODS: In this review, various applications of nanoflowers in biomedical researches and patents from various aspects have been investigated and reviewed. RESULTS: Nanoflowers attracted serious attentions in whole biomedical fields such as cardiovascular diseases, microbiology, sensors and biosensors, biochemical and cellular studies, cancer therapy, healthcare, etc. The competitive power of nanoflowers against other in use technologies provides successful achievements in the progress of mentioned biomedical studies. CONCLUSION: The use of nanoflowers in biomedicine leads to improving accuracy, reducing time to achieve the results, reducing costs, creating optimal treatment conditions as well as avoiding side effects of the treatment of specific diseases, and increasing functional strength.

A signal-on built in-marker electrochemical aptasensor for human prostate-specific antigen based on a hairbrush-like gold nanostructure.

A green electrodeposition method was firstly employed for the synthesis of round hairbrush-like gold nanostructure in the presence of cadaverine as a size and shape directing additive. The nanostructure which comprised of arrays of nanospindles was then applied as a transducer to fabricate a signal-on built in-marker electrochemical aptasensor for the detection of human prostate-specific antigen (PSA). The aptasensor detected PSA with a linear concentration range of 0.125 to 128 ng mL-1 and a limit of detection of 50 pg mL-1. The aptasensor was then successfully applied to detect PSA in the blood serum samples of healthy and patient persons.

Effect of Magnetic Fluid Hyperthermia on Implanted Melanoma in Mouse Models.

BACKGROUND: Nowadays, magnetic nanoparticles (MNPs) have received much attention because of their enormous potentials in many fields such as magnetic fluid hyperthermia (MFH). The goal of hyperthermia is to increase the temperature of malignant cells to destroy them without any lethal effect on normal tissues. To investigate the effectiveness of cancer therapy by magnetic fluid hyperthermia, Fe0.5Zn0.5Fe2O4 nanoparticles (FNPs) were used to undergo external magnetic field (f=515 kHz, H=100 G) in mice bearing implanted tumor. METHODS: FNPs were synthesized via precipitation and characterized using transmission electron microscopy (TEM), vibrating sample magnetometer, and Fourier transform infrared. For in vivo study, the mice bearing implanted tumor were divided into four groups (two mice per group), namely, control group, AMF group, MNPs group, and MNPs&AMF group. After 24 hours, the mice were sacrificed and each tumor specimen was prepared for histological analyses. The necrotic surface area was estimated by using graticule (Olympus, Japan) on tumor slides. RESULTS: The mean diameter of FNPs was estimated around 9 nm by TEM image and M versus H curve indicates that this particle is among superparamagnetic materials. According to histological analyses, no significant difference in necrosis extent was observed among the four groups. CONCLUSION: FNPs are biocompatible and have a good size for biomedical applications. However, for MFH approach, larger diameters especially in the range of ferromagnetic particles due to hysteresis loss can induce efficient heat in the target region.

Nanoporous nickel microspheres: synthesis and application for the electrocatalytic oxidation and determination of acyclovir.

Nickel microspheres were synthesized via a water-in-oil reverse nanoemulsion system using nickel nitrate as the nickel precursor and hydrazine hydrate as the reducing agent. The nanoemulsion was a triton X-100/cyclohexane/water ternary system. The surface morphology of the nickel microspheres was studied by scanning electron microscopy, which indicated that the microspheres had a nanoporous structure. The electrochemical behavior of the nanoporous nickel microspheres were studied in alkaline solution and were then employed to fabricate a modified carbon paste electrode in order to investigate the electrocatalytic oxidation of the drug acyclovir. The oxidation process involved, and its kinetics were investigated using cyclic voltammetry and chronoamperometry. The rate constant of the catalytic oxidation of acyclovir and the electron-transfer coefficient are reported. A sensitive, simple and time-saving amperometric procedure was developed for the analysis of acyclovir. The proposed amperometric method was also applied to determine acyclovir in tablets and topical cream.

Advances in iron chelation: an update.

INTRODUCTION: Oxidative stress (caused by excess iron) can result in tissue damage, organ failure and finally death, unless treated by iron chelators. The causative factor in the etiology of a variety of disease states is the presence of iron-generated reactive oxygen species (ROS), which can result in cell damage or which can affect the signaling pathways involved in cell necrosis-apoptosis or organ fibrosis, cancer, neurodegeneration and cardiovascular, hepatic or renal dysfunctions. Iron chelators can reduce oxidative stress by the removal of iron from target tissues. Equally as important, removal of iron from the active site of enzymes that play key roles in various diseases can be of considerable benefit to the patients. AREAS COVERED: This review focuses on iron chelators used as therapeutic agents. The importance of iron in oxidative damage is discussed, along with the three clinically approved iron chelators. EXPERT OPINION: A number of iron chelators are used as approved therapeutic agents in the treatment of thalassemia major, asthma, fungal infections and cancer. However, as our knowledge about the biochemistry of iron and its role in etiologies of seemingly unrelated diseases increases, new applications of the approved iron chelators, as well as the development of new iron chelators, present challenging opportunities in the areas of drug discovery and development.