Graphene quantum dots unraveling: Green synthesis, characterization, radiolabeling with 99mTc, in vivo behavior and mutagenicity.

Graphene is one of the crystalline forms of carbon, along with diamond, graphite, carbon nanotubes, and fullerenes, and is considered as a revolutionary and innovating product. The use of a graphene-based nanolabels is one of the latest and most prominent application of graphene, especially in the field of diagnosis and, recently, in loco radiotherapy when coupled with radioisotopes. However, its biological behavior and mutagenicity in different cell or animal models, as well as the in vivo functional activities, are still unrevealed. In this study we have developed by a green route of synthesizing graphene quantum dots (GQDs) and characterized them. We have also developed a methodology for direct radiolabeling of GQDs with radioisotopes.Finally; we have evaluated in vivo biological behavior of GQDs using two different mice models and tested in vitro mutagenicity of GQDs. The results have shown that GQDs were formed with a size range of 160-280 nm, which was confirmed by DRX and Raman spectroscopy analysis, corroborating that the green synthesis is an alternative, environmentally friendly way to produce graphene. The radiolabeling test has shown that stable radiolabeled GQDs can be produced with a high yield (>90%). The in vivo test has demonstrated a ubiquitous behavior when administered to healthy animals, with a high uptake by liver (>26%) and small intestine (>25%). Otherwise, in an inflammation/VEGF hyperexpression animal model (endometriosis), a very peculiar behavior of GQDs was observed, with a high uptake by kidneys (over 85%). The mutagenicity test has demonstrated A:T to G:C substitutions suggesting that GQDs exhibits mutagenic activity.

Cytotoxicity, genotoxicity, transplacental transfer and tissue disposition in pregnant rats mediated by nanoparticles: the case of magnetic core mesoporous silica nanoparticles.

Whether in the cosmetic or as therapeutic, the use of nanoparticles has been increasing and taking on global proportion. However, there are few studies about the physical potential of long-term use or use in special conditions such as chronic, AIDS, pregnant women and other special health circumstances. In this context, the study of the mutagenicity and the transplacental passage represents an important and reliable model for the primary evaluation of potential health risks, especially maternal and child health. In this study we performed mutagenicity, cytotoxic and transplacental evaluation of magnetic core mesoporous silica nanoparticles, radiolabeled with 99mTc for determination of toxicogenic and embryonic/fetuses potential risk in animal model. Magnetic core mesoporous silica nanoparticles were produced and characterized by obtaining nanoparticles with a size of (58.9 ± 8.1 nm) in spherical shape and with intact magnetic core. The 99 m Tc radiolabeling process demonstrated high efficacy and stability in 98% yield over a period of 8 hours of stability. Mutagenicity assays were performed using Salmonella enteric serovar Typhimurium standard strains TA98, TA100 and TA102. Cytotoxicity assays were performed using WST-1. The transplacental evaluation assays were performed using the in vivo model with rats in two periods: embryonic and fetal stage. The results of both analyzes corroborate that the nanoparticles can i) generate DNA damage; ii) generate cytotoxic potential and iii) cross the transplantation barrier in both stages and bioaccumulates in both embryos and fetuses. The results suggest that complementary evaluations should be conducted in order to attest safety, efficacy and quality of nanoparticles before unrestricted approval of their use.

Mutagenic and Cytotoxicity LQB 123 Profile: Safety and Tripanocidal Effect of a Phenyl-t-Butylnitrone Derivative.

The therapeutic options for Chagas disease are limited and its treatment presents a number of drawbacks including toxicity, drug resistance, and insufficient effectiveness against the chronic stage of the disease. Therefore, new therapeutical options are mandatory. In the present work, we evaluated the effect of a phenyl-tert-butylnitrone (PBN) derivate, LQB 123, against Trypanosoma cruzi forms. LQB 123 presented a trypanocidal effect against bloodstream trypomastigotes (IC50 = 259.4 ± 6.1 µM) and intracellular amastigotes infecting peritoneal macrophages (IC50 = 188.2 ± 47.5 µM), with no harmful effects upon the mammalian cells (CC50 values greater than 4 mM), resulting in a high selectivity index (CC50/IC50 > 20). Additionally, metacyclic trypomastigotes submitted to LQB 123 presented an IC50 of about 191.8 ± 10.5 µM and epimastigotes forms incubated with different concentrations of LQB 123 presented an inhibition of parasite growth with an IC50 of 255.1 ± 3.6 µM. Finally, we investigated the mutagenic potential of the nitrone by the Salmonella/microsome assay and observed no induction of mutagenicity even in concentrations as high as 33000 µM. Taken together, these results present a nonmutagenic compound, with trypanocidal activity against all relevant forms of T. cruzi, offering new insights into CD treatment suggesting additional in vivo tests.

Cellular inactivation induced by H2O2 and active oxygen species generated by environmental stresses in bacteria

Oxyygen free radicals are highly reactive species that damage several cellular macromolecules and organelles, including membrane lipid peroxidation and produce DNA lesions. We have discussed here; i) The mechanism of radiation-induced cellular damage in bacteria through the intermediation of active oxygen species; ii) the cellular inactivation and the role of bacterial SOS and OxyR systems in the repair of lesions induced by H2O2 under low iron condition; iii) the lethal interaction between H2O2 and o-phenanthroline in E. coli; iv) the biological response induced by near-UV radiation mediated by active oxygen species and finally v) the mutagenic potential of popular plant extracts like guaraná (Paullinia cupana), mate (Ilex paraguariensis) and saiao (Kalanchoe brasiliensis), whose effects are eventually mediated by active oxygen species.