Amedea B. Seabra

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

Silver nanoparticles: A new view on mechanistic aspects on antimicrobial activity

UNLABELLED Silver nanoparticles are well known potent antimicrobial agents. Although significant progresses have been achieved on the elucidation of antimicrobial mechanism of silver nanoparticles, the exact mechanism of action is still not completely known. This overview incorporates a retrospective of previous reviews published and recent original contributions on the progress of research on antimicrobial mechanisms of silver nanoparticles. The main topics discussed include release of silver nanoparticles and silver ions, cell membrane damage, DNA interaction, free radical generation, bacterial resistance and the relationship of resistance to silver ions versus resistance to silver nanoparticles. The focus of the overview is to summarize the current knowledge in the field of antibacterial activity of silver nanoparticles. The possibility that pathogenic microbes may develop resistance to silver nanoparticles is also discussed. FROM THE CLINICAL EDITOR Antibacterial effect of nanoscopic silver generated a lot of interest both in research projects and in practical applications. However, the exact mechanism is still will have to be elucidated. This overview incorporates a retrospective of previous reviews published from 2007 to 2013 and recent original contributions on the progress of research on antimicrobial mechanisms to summarize our current knowledge in the field of antibacterial activity of silver nanoparticles.

Nitric oxide-releasing vehicles for biomedical applications

Nitric oxide (NO) is involved in several physiological processes, such as the control of vascular tone, the inhibition of platelet aggregation, smooth muscle cell replication, the immune response, and wound healing processes. Several pathologies have been associated with dysfunctions in the endogenous production of NO. Thus, there is great interest in developing NO-releasing drugs and in matrices which are able to stabilize and release NO locally and directly in different tissues. Over the past few years, a very promising strategy for biocompatible NO-delivery systems has emerged based on the use of nanobiotechnology for targeted NO-release for biomedical applications. In this work, the current state-of-the-art approaches to NO-release from nanomeric materials, their preparation, and promising biomedical applications are reviewed. Such materials, comprised of dendrimers, liposomes, metallic and silica nanoparticles, polymeric micro and nanoparticles, semiconductor quantum dots, carbon nanotubes, and nanoporous solid materials exhibit exceptional potential in directly delivering NO in a controlled spatial and temporal manner with superior biocompatibility for pharmacological applications.

Thermal and photochemical nitric oxide release from S-nitrosothiols incorporated in Pluronic F127 gel: potential uses for local and controlled nitric oxide release

The local delivery of nitric oxide (nitrogen monoxide, NO) by thermal or photochemical means to target cells or organs has a great potential in several biomedical applications, especially if the NO donors are incorporated into non-toxic viscous matrices. In this work, we have shown that the NO donors S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC) can be incorporated into F127 hydrogels, from where NO can be released thermally or photochemically (with lambda(irr)>480nm). High sensitivity differential scanning calorimetry (HSDSC) and a new spectrophotometric method, were used to characterize the micellization and the reversal thermal gelation processes of the F127 hydrogels containing NO donors, and to modulate the gelation temperatures to the range 29-32 degrees C. Spectral monitoring of the S-NO bond cleavage showed that the initial rates of thermal and photochemical NO release (ranging from 2 to 45 micromoll(-1)min(-1)) are decreased in the hydrogel matrices, relative to those obtained in aqueous solutions. This stabilization effect was assigned to a cage recombination mechanism and offers an additional advantage for the storage and handling of S-nitrosothiols. These results indicate that F127 hydrogels might be used for the thermal and photochemical delivery of NO from S-nitrosothiols to target areas in biomedical applications.

Topically applied S-nitrosothiol-containing hydrogels as experimental and pharmacological nitric oxide donors in human skin

Background  Nitric oxide (NO) has a wide range of functions in the skin, and topical NO donors have several potential clinical applications. However, currently available donors are either unstable on the skin surface, release low concentrations of NO, or have a short duration of action. Endogenous S‐nitrosothiols (RSNOs) store and transport NO within the body and can be used as exogenous sources of NO.

S-nitrosoglutathione-containing hydrogel accelerates rat cutaneous wound repair

Background  Nitric oxide (NO) plays a key role in wound repair and S‐nitrosothiols like S‐nitrosoglutathione (GSNO) are well known NO donors.

Antibacterial Nitric Oxide‐Releasing Polyester for the Coating of Blood‐Contacting Artificial Materials

The emergence of multidrug-resistant bacteria associated with blood-contacting artificial materials is a growing health problem, which demands new approaches in the field of biomaterials research. In this study, a poly(sulfhydrylated polyester) (PSPE) was synthesized by the polyesterification reaction of mercaptosuccinic acid with 3-mercapto-1,2-propanediol and blended with poly(methyl methacrylate) (PMMA) from solution, leading to solid PSPE/PMMA films, with three different PSPE : PMMMA mass ratios. These films were subsequently S-nitrosated through the immersion in acidified nitrite solution, yielding poly(nitrosated)polyester/PMMA (PNPE/PMMA) films. A polyurethane intravascular catheter coated with PNPE/PMMA was shown to release nitric oxide (NO) in phosphate buffered saline solution (pH 7.4) at 37 degrees C at rates of 4.6 nmol/cm(2)/h in the first 6 h and 0.8 nmol/cm(2)/h in the next 12 h. When used to coat the bottom of culture plates, NO released from these films exerted a potent dose- and time-dependent antimicrobial activity against Staphylococcus aureus and a multidrug-resistant Pseudomonas aeruginosa strains. This antibacterial effect of PSPE/PMMA films opens a new perspective for the coating of blood-contacting artificial materials, for avoiding their colonization with highly resistant bacteria.

Nitric oxide donor improves healing if applied on inflammatory and proliferative phase

BACKGROUND Nitric oxide (NO) is an important molecule synthesized during wound repair. Studies have reported the use of NO donors on cutaneous wound repair, but their effects in different phases of healing are still not elucidated. The aim of this work was to investigate the effects of topical application of a NO donor (S-nitrosoglutathione, GSNO)-containing hydrogel on excisional wounds in the inflammatory ((inf)), proliferative ((prol)), and inflammatory and proliferative phases ((inf+prol)) of rat cutaneous wound repair. MATERIAL AND METHODS In each group (control, GSNO(inf), GSNO(prol), and GSNO(inf+prol)), excisional wounds on the dorsal surface were made and wound contraction and re-epithelialization were evaluated. Fourteen days after wounding, wounds and adjacent skin were formalin-fixed and paraffin-embedded. Collagen fibers organization, mast cells, myofibroblasts and vessels were evaluated. RESULTS Wound contraction of the GSNO(inf+prol) group was faster than control, GSNO(inf), and GSNO(prol) groups, 5 and 7 d after wounding. Topical application of GSNO accelerated re-epithelialization 14 d after wounding, mainly in GSNO(inf+prol) group. In addition, the GSNO(inf+prol) group showed improved collagen fibers maturation and tissue organization, and lower amount of inflammatory cells in the superficial and deep areas of the granulation tissue, compared with the other groups. CONCLUSIONS NO is important in all phases of rat cutaneous wound repair, but if applied on inflammatory and proliferative phases, the improvement in wound healing (accelerating wound closure, wound re-epithelialization, and granulation tissue organization) is more impressive.

Biogenic nanoparticles: copper, copper oxides, copper sulphides, complex copper nanostructures and their applications.

Copper nanoparticles have been the focus of intensive study due to their potential applications in diverse fields including biomedicine, electronics, and optics. Copper-based nanostructured materials have been used in conductive films, lubrification, nanofluids, catalysis, and also as potent antimicrobial agent. The biogenic synthesis of metallic nanostructured nanoparticles is considered to be a green and eco-friendly technology since neither harmful chemicals nor high temperatures are involved in the process. The present review discusses the synthesis of copper nanostructured nanoparticles by bacteria, fungi, and plant extracts, showing that biogenic synthesis is an economically feasible, simple and non-polluting process. Applications for biogenic copper nanoparticles are also discussed.