Renata de Lima

Nanotoxicity of Graphene and Graphene Oxide

Graphene and its derivatives are promising candidates for important biomedical applications because of their versatility. The prospective use of graphene-based materials in a biological context requires a detailed comprehension of the toxicity of these materials. Moreover, due to the expanding applications of nanotechnology, human and environmental exposures to graphene-based nanomaterials are likely to increase in the future. Because of the potential risk factors associated with the manufacture and use of graphene-related materials, the number of nanotoxicological studies of these compounds has been increasing rapidly in the past decade. These studies have researched the effects of the nanostructural/biological interactions on different organizational levels of the living system, from biomolecules to animals. This review discusses recent results based on in vitro and in vivo cytotoxicity and genotoxicity studies of graphene-related materials and critically examines the methodologies employed to evaluate their toxicities. The environmental impact from the manipulation and application of graphene materials is also reported and discussed. Finally, this review presents mechanistic aspects of graphene toxicity in biological systems. More detailed studies aiming to investigate the toxicity of graphene-based materials and to properly associate the biological phenomenon with their chemical, structural, and morphological variations that result from several synthetic and processing possibilities are needed. Knowledge about graphene-based materials could ensure the safe application of this versatile material. Consequently, the focus of this review is to provide a source of inspiration for new nanotoxicological approaches for graphene-based materials.

Silver nanoparticles: a brief review of cytotoxicity and genotoxicity of chemically and biogenically synthesized nanoparticles.

In recent years interest in silver nanoparticles and their applications has increased mainly because of the important antimicrobial activities of these nanomaterials, allowing their use in several industrial sectors. However, together with these applications, there is increasing concerning related to the biological impacts of the use of silver nanoparticles on a large scale, and the possible risks to the environment and health. In this scenario, some recent studies have been published based on the investigation of potential inflammatory effects and diverse cellular impacts of silver nanoparticles. Another important issue related to nanoparticle toxicity in biological media is the capacity for increased damage to the genetic material, since nanoparticles are able to cross cell membranes and reach the cellular nucleus. In this regard, there is increasing interest in the analysis of potential nanoparticle genotoxicity, including the effects of different nanoparticle sizes and methods of synthesis. However, little is known about the genotoxicity of different silver nanoparticles and their effects on the DNA of organisms; thus further studies in this field are required. This mini‐review aims to present and to discuss recent publications related to genotoxicity and the cytotoxicity of silver nanoparticles in order to better understand the possible applications of these nanomaterials in a safe manner. This present work concludes that biogenic silver nanoparticles are generally less cyto/genotoxic in vivo compared with chemically synthesized nanoparticles. Furthermore, human cells were found to have a greater resistance to the toxic effects of silver nanoparticles in comparison with other organisms. Copyright

Preparation, characterization, cytotoxicity, and genotoxicity evaluations of thiolated- and s-nitrosated superparamagnetic iron oxide nanoparticles: implications for cancer treatment.

Iron oxide magnetic nanoparticles have been proposed for an increasing number of biomedical applications, such as drug delivery. To this end, toxicological studies of their potent effects in biological media must be better evaluated. The aim of this study was to synthesize, characterize, and examine the potential in vitro cytotoxicity and genotoxicity of thiolated (SH) and S-nitrosated (S-NO) iron oxide superparamagnetic nanoparticles toward healthy and cancer cell lines. Fe3O4 nanoparticles were synthesized by coprecipitation techniques and coated with small thiol-containing molecules, such as mercaptosuccinic acid (MSA) or meso-2,3-dimercaptosuccinic acid (DMSA). The physical-chemical, morphological, and magnetic properties of thiol-coating Fe3O4 nanoparticles were characterized by different techniques. The thiol groups on the surface of the nanoparticles were nitrosated, leading to the formation of S-nitroso-MSA- or S-nitroso-DMSA-Fe3O4 nanoparticles. The cytotoxicity and genotoxicity of thiolated and S-nitrosated nanoparticles were more deeply evaluated in healthy (3T3, human lymphocytes cells, and chinese hamster ovary cells) and cancer cell lines (MCF-7). The results demonstrated that thiol-coating iron oxide magnetic nanoparticles have few toxic effects in cells, whereas S-nitrosated-coated particles did cause toxic effects. Moreover, due to the superaramagnetic behavior of S-nitroso-Fe3O4 nanoparticles, those particles can be guided to the target site upon the application of an external magnetic field, leading to local toxic effects in the tumor cells. Taken together, the results suggest the promise of S-nitroso-magnetic nanoparticles in cancer treatment.

Nitric oxide releasing nanomaterials for cancer treatment: current status and perspectives.

Nitric oxide (NO) is known to have dichotomous effects on cancer biology, acting as a pro- or antineoplastic agent. Low concentrations of NO are reported to promote tumor growth, whereas high NO influx acts as a potent tumor repressor, leading to cytotoxicity and apoptosis. There is increasing interest in developing NO-releasing materials as potent tumoricidal agents in which high and localized concentrations of NO may be directly released in a sustained manner to the tumor site. Nanomaterials allied to NO donors have emerged as a promising strategy in cancer treatment. In this context, this review summarizes the roles of NO in cancer biology and highlights the therapeutic potential effects of NO-releasing nanomaterials based on polymeric nanoparticles, dendritic polymers, liposomes, silica nanoparticles, metallic nanoparticles and quantum dots in combating tumor cells.

Cytotoxicity and Genotoxicity of Biogenically Synthesized Silver Nanoparticles

In recent years, the development of nanotechnology has been focused on the development of protocols to synthesize important technological and medical metallic nanoparticles, such as silver nanoparticles, based on clean, nontoxic, biocompatible, and environmentally friendly approaches. “Green” synthesis of nanoparticles can be successfully performed extracellularly or intracellularly by organisms such as bacteria, yeast, fungi, algae, and plant extracts. Only in the recent past, biogenic syntheses of metal nanoparticles have gained significant attention. Silver nanoparticles (AgNPs) are considered one of the most important and commonly used metallic nanoparticles, in particular in medical applications, due to their known antimicrobial activities. In this scenario, this chapter discusses the recent developments on the biogenic synthesis of AgNPs by bacteria, yeast, fungi, algae and plants, highlighting the advantages and drawbacks of biogenic syntheses methods. Moreover, in order to propose any biological applications of AgNPs, it is mandatory to detailed investigate the toxicity of this nanomaterial. In this context, this chapter also discusses recent progress on the in vitro and in vivo cytotoxicity and genotoxicity of biogenic and chemically synthesized AgNPs. Although important progresses have been reached in this domain, there is still a necessity of more and detailed studies on the toxicity of AgNPs, in particular on biogenic AgNPs. Therefore, this chapter hopes to be a source of inspiration for more studies on the biogenic syntheses of AgNPs and the fully characterization of their toxic effects on humans and on the environment.

Nanocapsules Containing Neem ( Azadirachta Indica ) Oil: Development, Characterization, And Toxicity Evaluation

In this study, we prepared, characterized, and performed toxicity analyses of poly(ε-caprolactone) nanocapsules loaded with neem oil. Three formulations were prepared by the emulsion/solvent evaporation method. The nanocapsules showed a mean size distribution around 400 nm, with polydispersity below 0.2 and were stable for 120 days. Cytotoxicity and genotoxicity results showed an increase in toxicity of the oleic acid + neem formulations according to the amount of oleic acid used. The minimum inhibitory concentrations demonstrated that all the formulations containing neem oil were active. The nanocapsules containing neem oil did not affect the soil microbiota during 300 days of exposure compared to the control. Phytotoxicity studies indicated that NC_20 (200 mg of neem oil) did not affect the net photosynthesis and stomatal conductance of maize plants, whereas use of NC_10 (100:100 of neem:oleic acid) and NC_15 (150:50 of neem:oleic acid) led to negative effects on these physiological parameters. Hence, the use of oleic acid as a complement in the nanocapsules was not a good strategy, since the nanocapsules that only contained neem oil showed lower toxicity. These results demonstrate that evaluation of the toxicity of nanopesticides is essential for the development of environmentally friendly formulations intended for applications in agriculture.

Genetic Studies on the Effects of Nanomaterials

The aim of this chapter is to present some of the principal methodologies used to study the effects of toxic substances on DNA, which can be used to analyze aspects of nanomaterial toxicity. It is not the intention here to undertake an in-depth survey of the topic, but rather to highlight the techniques that can be used in nanotoxicity studies. The available methods for evaluating effects on DNA include genotoxicity tests such as (1) the Allium cepa chromosome aberration test, (2) the comet analysis, (3) the micronucleus test, and (4) the cytogenetic analysis. In addition, this chapter also described the methodologies for analysis of gene expression that can be applied to the effects of nanomaterials. A description of the characteristics of each method is provided, together with results of selected studies that have evaluated the effects of nanomaterials, and a critical discussion of the main advantages and disadvantages of each technique. The chapter also highlights the challenges and future perspectives for studies of the effects of nanostructured materials on DNA.

Analysis of the effects of pesticides and nanopesticides on the environment

One of the main consequences of population growth is that an equivalent food production increase is needed. To meet this basic need of society and ensure growth in food production, it is necessary the use of agrochemicals such as herbicides, preventing competition between crops and weeds for soil nutrients. This growth in use of agrochemicals has historically had undesirable consequences due to their indiscriminate and sometimes reckless use, with health problems for farmers and environmental damage. One of the possible solutions to increase agricultural production without these consequences would be the application of nanotechnology to allow a safer use of pesticides and lessen health and environmental side-effects. However, the use of nanotechnology demands an investigation of possible toxic effects of this technology, mainly in relation to contamination of soil and water. The study we performed aimed to produce nanoparticles containing the herbicide paraquat and to analyze its possible genotoxic effects. The technique used was cytogenetic test of Allium cepa treated with nanoparaquat, conventional paraquat, tripolyphosphate chitosan nanoparticles, which were made in duplicate with and without humic substances. All concentrations were 0,38 mg.mL-1, and negative control was made with ultrapure water and humic substances for comparative purposes. Initial results indicated less chromosome damage in nanoparaquat treated samples compared to conventional paraquat herbicide, indicating that nanoencapsulation is a viable option as an attempt to minimize damage caused by paraquat.