Enhanced anticancer activity of silver doped zinc oxide magnetic nanocarrier loaded with sorafenib for hepatocellular carcinoma treatment.

Drug delivery is the process or method of delivering a pharmacological product to have therapeutic effects on humans or animals. The use of nanoparticles to deliver medications to cells is driving the present surge in interest in improving human health. Green nanodrug delivery methods are based on chemical processes that are acceptable for the environment or that use natural biomaterials such as plant extracts and microorganisms. In this study, zinc oxide-superparamagnetic iron oxide-silver nanocomposite was synthesized via green synthesis method using Fusarium oxysporum fungi mycelia then loaded with sorafenib drug. The synthesized nanocomposites were characterized by UV-visibile spectroscopy, FTIR, TEM and SEM techniques. Sorafenib is a cancer treatment and is also known by its brand name, Nexavar. Sorafenib is the only systemic medication available in the world to treat hepatocellular carcinoma. Sorafenib, like many other chemotherapeutics, has side effects that restrict its effectiveness, including toxicity, nausea, mucositis, hypertension, alopecia, and hand-foot skin reaction. In our study, 40 male albino rats were given a single dose of diethyl nitrosamine (DEN) 60 mg/kg b.wt., followed by carbon tetrachloride 2 ml/kg b.wt. twice a week for one month. The aim of our study is using the zinc oxide-superparamagnetic iron oxide-silver nanocomposite that was synthesized by Fusarium oxysporum fungi mycelia as nanocarrier for enhancement the sorafenib anticancer effect.

Green synthesis of nano-based drug delivery systems developed for hepatocellular carcinoma treatment: a review.

This review presents an overview of one of the effective strategies for improving the anticancer impact of many drugs including sorafenib using a drug delivery system by employing nanoparticles that is produced through a biological system. The biological process has a lot of benefits, including being inexpensive and safe for the environment. Sorafenib is one of a multi-kinase inhibitor that inhibits molecularly targeted kinases. Because of its poor pharmacokinetic characteristics, such as fast elimination and limited water solubility, the bioavailability of Sorafenib is extremely low. More intelligent nano formulations of sorafenib have been developed to boost both the drug's target ability and bioavailability. Researchers in a wide variety of sectors, including nanomedicine, have recently been interested in the topic of nanotechnology. It is possible for the body to develop resistance to widely used drugs available for treatment of liver cancer, including sorafenib. As a result, our goal of this research is to highlight the efficacy of nanomedicine-based drug delivery system to enhance drug's cancer-fighting properties. Because of their magnetic properties, certain nanoparticle materials can be employed as a carrier for the medicine to the exact place where the cancer is located. This can lower the amount of the drug that is administered with no impact on the normal cells.

An in vitro cytotoxicity of glufosfamide in HepG2 cells relative to its nonconjugated counterpart.

BACKGROUND: Glufosfamide (ß-D-glucosylisophosphoramide mustard, GLU) is an alkylating cytotoxic agent in which ifosforamide mustard (IPM) is glycosidically linked to the ß-D-glucose molecule. GLU exerted its cytotoxic effect as a targeted chemotherapy. Although, its cytotoxic efficacy in a number of cell lines, there were no experimental or clinical data available on the oncolytic effect of oxazaphosphorine drugs in hepatocellular carcinoma. Therefore, the main objective of the current study is to assess the cytotoxic potential of GLU for the first time in the hepatocellular carcinoma HepG2 cell line model. METHODS: Cytotoxicity was assayed by the MTT method, and half-maximal inhibitory concentration (IC50) was calculated. Flow cytometric analysis of apoptosis frequencies was measured by using Annexin V/PI double stain, an immunocytochemical assay of caspase-9, visualization of caspase-3, and Bcl2 gene expression were undertaken as apoptotic markers. Mitochondrial membrane potential was measured using the potentiometric dye; JC-1, as a clue for early apoptosis as well as ATP production, was measured by the luciferase-chemiluminescence assay. RESULTS: Glufosfamide induced cytotoxicity in HepG2 cells in a concentration- and time-dependent manner. The IC50 values for glufosfamide were significantly lower compared to ifosfamide. The frequency of apoptosis was much higher for glufosfamide than that of ifosfamide. The contents of caspase-9 and caspase-3 were elevated following exposure to GLU more than IFO. The anti-apoptotic Bcl2 gene expression, the mitochondrial membrane potential, and the cellular ATP levels were significantly decreased than in case of ifosfamide. CONCLUSIONS: The current study reported for the first time cytotoxicity activity of glufosfamide in HepG2 cells in vitro. The obtained results confirmed the higher oncolytic activity of glufosfamide than its aglycone ifosfamide. The generated data warrants further elucidations by in vivo study.

Assessment of Thyroid Function and Oxidative Stress State in Foundry Workers Exposed to Lead.

BACKGROUND: Exposure to lead (Pb) has been associated with endocrine, hematological, gastrointestinal, renal and neurological problems in humans. However, effects on the thyroid gland are controversial. OBJECTIVES: The aim of the present study was to assess thyroid function in foundry workers occupationally exposed to Pb and the mechanism of oxidative-antioxidant imbalance. METHODS: Thyroid function parameters and markers of oxidative stress were examined in 59 adult males who had been occupationally exposed to Pb. The results were then compared to those of 28 male subjects who had no history of Pb exposure or thyroid abnormalities and served as a control group. RESULTS: Mean blood lead levels (16.5±1.74 µg/dl) were significantly higher among the exposed workers compared to those of the control group (12.8±1.16 µg/dl, (p <0.001)). The exposed group had significantly increased free triiodothyronine (FT3), free thyroxine (FT4) and significantly decreased thyroid stimulating hormone (TSH) (1.77±0.44 µIU/ml), whereas the control group had a TSH level of 2.61±0.94 µIU/ml (p< 0.0001). A state of oxidative stress was indicated by the significant increase in mean levels of malondialdehyde (MDA) and significant decrease in glutathione (GSH) (p < 0.0001). There was a significant positive correlation (r=0.358, p <0.05) between blood lead levels (BLL) and duration of employment, while BLL showed a significant negative correlation with TSH (r =-0.486, p <0.001), and GSH (r =-0.336, p <0.05). Of the occupationally exposed workers, 32.76% had elevated thyroid hormones. The results showed a significant positive relationship between GSH and TSH (ß coefficient=0.274, p < 0.05), MDA with FT3 (ß coefficient=0.355, p < 0.05) and FT4 (ß coefficient = 0.491, p < 0.0001) among exposed workers. CONCLUSIONS: Workers exposed to Pb dust proved to be at risk for hyperthyroidism, which was found to have a significant role in oxidative-antioxidant imbalance present among workers with increasing duration of exposure. PARTICIPANT CONSENT: Obtained. ETHICS APPROVAL: This study was approved by the Ethical Committee of the National Research Centre in Egypt (NRC) under the registration number 15225. COMPETING INTERESTS: The authors declare no competing financial interests.

Solid-state fermentation for enhanced production of selenium nanoparticles by gamma-irradiated Monascus purpureus and their biological evaluation and photocatalytic activities.

Selenium nanoparticles (SeNPs) were successfully synthesized using the culture extract of Monascus purpureus ATCC16436 grown on sugarcane bagasse under solid-state fermentation. The rapid synthesis of SeNPs was completed after 30 min as confirmed by UV-Vis spectroscopy. Functional groups present in the synthesized SeNPs samples were confirmed by Fourier transform infrared spectroscopy. The synthesized SeNPs showed a single-phase crystalline structure. Transmission electron microscope revealed the spherical shape and the mean particle size was 46.58 nm. Dynamic light scattering analysis showed that the synthesized SeNPs were monodispersed and the recorded polydispersity index value was 0.205. Zeta potential value of - 24.01 mV indicated the high stability of SeNPs. Besides, the biological activities of antioxidant, anticancer and antimicrobial as well as the photocatalytic activities were also studied. SeNPs showed promising antioxidant activity with 50% inhibitory concentration of 85.92 µg mL-1. Based on the MTT assay, SeNPs inhibited the proliferation of normal human melanocytes, human breast and liver cancer cell lines with 50% inhibitory concentrations of 45.21, 61.86 and 200.15 µg mL-1, respectively. SeNPs showed broad spectrum of antimicrobial potential against the tested human and plant pathogens. SeNPs showed efficient degradation of methylene blue dye. Moreover, the effect of gamma irradiation on the production enhancement of SeNPs was also adopted. Exposure of the fungal spores to gamma rays at 1000 Gy increased the yield of SeNPs to approximately fivefold. Hence, this study suggests a new and alternate approach with the excellent biotechnological potentiality for the production of SeNPs.

Extracellular biosynthesis of cobalt ferrite nanoparticles by Monascus purpureus and their antioxidant, anticancer and antimicrobial activities: Yield enhancement by gamma irradiation.

Cobalt ferrite nanoparticles were successfully synthesized using the fungus Monascus purpureus ATCC16436 as a potentially low-cost, eco-friendly and easy to produce method. Fourier transform infrared spectroscopy confirmed the functional groups present in the prepared samples. X-ray diffraction pattern of the synthesized nanoparticles revealed a single-phase crystalline structure. Transmission electron microscope studies showed the spherical shape with a mean particle size of 6.50 nm. Vibrating sample magnetometer analyses revealed that the synthesized nanoparticles have a superparamagnetic behavior. In addition, the antioxidant, anticancer and antimicrobial activities of the synthesized nanoparticles were evaluated. The synthesized nanoparticles exhibited antioxidant potential as compared by ascorbic acid with 50% inhibitory concentration of 100.25 µg mL-1. Based on the MTT assay, the synthesized nanoparticles significantly inhibited the proliferation of two different human cancer cell lines (breast and liver) and normal human melanocytes. The recorded 50% inhibitory concentrations of the respective cell lines were 45.21, 61.86 and 200.15 µg mL-1. The synthesized nanoparticles showed potent antibacterial and antifungal activities against all the tested plant and human microbial pathogens with minimal inhibitory concentration range 250-500 µg mL-1. Moreover, the feasibility of production enhancement of the synthesized nanoparticles using the fungal culture as affected by gamma irradiation was also adopted. Gamma irradiation at 1000 Gy dramatically intensified the yield of nanoparticles to 24.87 g L-1. Accordingly, these findings suggest a new and alternate approach with the excellent biotechnological potentiality for the nanoparticles production that will open up the way for the industrial manufacture of nanomaterials.