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Antifungal and antimycotoxigenic activity of fullerenol nanoparticles (FNPs) were investigated on Aspergillus flavus growth isolated from a real food sample and aflatoxins (AFs) (AFB1 and AFB2 ) production. The final FNPs concentrations in in vitro and in commercial corn flour after the stationary incubation period of 7 and 14 days were in the range 0.16-80 µg/mL and 0.16-80 µg/g, respectively. Nanocharacterization of FNPs revealed an average size of 5-20 nm and a zeta potential of -35 mV. The highest degree of A. flavus mycelium growth inhibition (28%) after 7 days was observed for applied FNP concentration of 8.0 µg/mL, while after 14 days FNP concentration of 0.32 µg/mL led to the maximal inhibition of A. flavus mycelium growth (36%). Spearman's correlations analysis revealed a strong positive correlation between AFB1 and AFB2 concentrations in YES broth after 7 (R = 0.994, p < 0.05) and 14 days (R = 0.976), as well as between AFs concentrations and A. flavus mycelium mass after 7 (R = 0.786 for AFB1 and R = 0.766 for AFB2 ) and 14 days (R = 0.810 for AFB1 and R = 0.833 for AFB2 ). Paired samples t-test showed the existence of a statistically significant difference (p < 0.05) between the produced AFs concentrations after the incubation of 7 and 14 days. Regarding the artificially inoculated corn flour the lower applied FNP concentrations (0.16-0.8 µg/g) achieved a reduction of AFB1 up to 42% and 60% after 7 and 14 days, respectively.

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Helicobacter pylori (H. pylori) eradication by antibiotics and proton pump inhibitor treatment is limited by the low pH microenvironment in the stomach and can lead to antibiotic resistance. We fabricated fullerenol nanoparticles (FNPs) with varied chemical structures responding to a pinacol rearrangement of vicinal hydroxyl to form carbonyls in low pH environments. An obvious increase in C═O/C-O was induced in low pH and was positively correlated with a peroxidase-like activity. The FNPs exerted an excellent effect on H. pylori eradication in vitro and in vivo because of their peroxidase-like activity. FNP treatment of a H. pylori biofilm revealed that FNPs broke down polysaccharides in cell wall components, resulting in collapse of the bacteria. The cycles of FNPs combining and dissociating with the peroxidase substrate were detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and confirmed that FNPs enhance peroxidase-like activity. Further, the isothermal titration calorimetry results showed that FNPs with more C═O/C-O had greater affinity to bind the peroxidase substrates. Therefore, we suggest that varied C═O/C-O serves as a switch to respond to low pH in the stomach to kill H. pylori by inducing a peroxidase-like activity. FNPs can also overcome the challenge of antibiotic resistance to achieve H. pylori eradication in the stomach.

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We report the construction of blood cell membrane cloaked mesoporous silica nanoparticles for delivery of nanoparticles [fullerenols (Fols)] with fibrinolysis activity which endows the active Fol with successful thrombolysis effect in vivo. In vitro, Fols present excellent fibrinolysis activity, and the Fol with the best fibrinolysis activity is screened based on the correlation between Fols' structure and their fibrinolysis activity. However, the thrombolytic effect in vivo is not satisfactory. To rectify the unsatisfactory situation and avoid the exogenous stimuli, a natural blood cell membrane cloaking strategy with loading the active Fol is chosen to explore as a novel thrombolysis drug. After cloaking, the therapeutic platform prolongs blood circulation time and enhances the targeting effect. Interestingly, compared with platelet membrane cloaking, red blood cell (RBC) membrane cloaking demonstrates stronger affinity with fibrin and more enrichment at the thrombus site. The Fol with RBC cloaking shows quick and efficient thrombolysis efficacy in vivo with less bleeding risk, more excellent blood compatibility, and better biosafety when compared with the clinical drug urokinase (UK). These findings not only validate the blood cell membrane cloaking strategy as an effective platform for Fol delivery on thrombolysis treatment, but also hold a great promising solution for other active nanoparticle deliveries in vivo.

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The enormous progress in nanomaterials development and their use, followed by their inevitable environmental print, has arisen the emerging questions concerning their influence to the living systems. Honey bees are considered to be quite a suitable model system for the risk assessment and prediction of various external influences. To the best of our knowledge, this is the first study dealing with the influence of fullerenol nanoparticles (FNP), a biodegradable carbon nanomaterials' representative, to honey bees. This investigation was conducted with an aim to merge two different open-ended questions: the potential toxic effect of FNP to the bees on the one hand and antioxidative effect of FNP on the other hand. Since FNP antioxidative properties were proved in a number of in vivo models, we hypothesized the similar outcomes, and according to this assumption, we opted for paraquat as a well-known oxidative stress inducer. FNP did not have toxic effect in none of investigated concentrations. The results also confirmed the potential of FNP to reduce oxidative stress through the gene expression of antioxidative enzymes and the change in the redox state of the cells. Additional experiments are needed for a better understanding of the exact mechanism and complex patterns of FNP's activity.

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BACKGROUND: Tumor metastasis is the primary cause of mortality in cancer patients. Migratory breast cancer cells in lymphatic and blood vessels seek new sites and form metastatic colonies in the lung and bone, and then these cancer cells often wreak considerable havoc. With advances in nanotechnology, nanomaterials and nanotechnologies are widely applied in tumor therapy. In this paper, small size fullerenol nanoparticles, which are separated by isoelectric focusing electrophoresis (IFE) for discrepancy of isoelectric point (pI), are used in the study of tumor metastasis. RESULTS: In this study, the commendable inhibition of tumor metastasis was uncovered by intravenous injection of purified fullerenol fraction with special surface charge and functional groups, which was separated by IFE for discrepancy of pI. By investigating the actin dynamics in several cancer cell lines, we found these small size fullerenol nanoparticles disturbed actin dynamics. Young's modulus detection and cell migration assays revealed that fullerenol lowered stiffness and restrained migration of breast cancer cells. Filopodia, the main supporting structures of actin bundles, are important for cell motility and adhesion. Scanning electron microscopy showed that fullerenol reduced the number and length of filopodia. Simultaneously, the inhibition of integrin to form clusters on filopodias, which was likely induced by reorganizing of actin cytoskeleton, impacted cancer cell adhesion and motility. CONCLUSIONS: With intravenous injection of these fullerenol nanoparticles, tumor metastasis is well inhibited in vivo. The underlying mechanism most likely to be attributed to the effect of fullerenol nanoparticles on disturbing actin dynamics. With the disordered actin fiber, cell function is varied, including decreased cell stiffness, reduced filopodia formation, and inactivated integrin.

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Doxorubicin (DOX), commonly used antineoplastic agent, affects bone marrow, intestinal tract and heart, but it also has some hepatotoxic effects. Main mechanism of its toxicity is the production of free reactive oxygen species. Polyhidroxilated C60 fullerene derivatives, fullerenol nanoparticles (FNP), act as free radical scavengers in in vitro systems. The aim of the study was to investigate potential FNP protective role against DOX-induced hepatotoxicity in rats. Experiments were performed on adult male Wistar rats. Animals were divided into five groups: (1) 0.9% NaCl (control), (2) 100mg/kg ip FNP, (3) 10mg/kg DOX iv, (4) 50mg/kg ip FNP 30min before 10mg/kg iv DOX, (5) 100mg/kg ip FNP 30min before 10mg/kg iv DOX. A general health condition, body and liver weight, TBARS level and antioxidative enzyme activity, as well as pathohistological examination of the liver tissue were conducted on days 2 and 14 of the study. FNP, applied alone, did not alter any examinated parameters. However, when used as a pretreatment it significantly increased survival rate, body and liver weight, and decreased TBARS level, antioxidative enzyme activity and hepatic damage score in DOX-treated rats. FNP administered at a dose of 100mg/kg significantly attenuated effects of doxorubicin administered in a single high dose in rats, concerning general condition, body and liver weight, lipid peroxidation level and antioxidative enzyme activity as well as structural alterations of the hepatic tissue.

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