Os efeitos malignos dos efluentes industriais tóxicos no meio ambiente têm aumentado consideravelmente nas últimas décadas. Maior atenção tem sido empregada à contaminação das águas, devido à sua importância no controle da vida na Terra e por 70% de sua superfície ser constituída por água. A fotocatálise heterogênea surge como uma boa alternativa na remediação dos males causados pelos efluentes. Óxidos semicondutores e nanoestruturados, como aqueles de cério e titânio são extensivamente estudados devido às suas propriedades optoeletrônicas, além da estabilidade química e térmica. Pequenas mudanças na estrutura e na morfologia de materiais podem acarretar no aperfeiçoamento das propriedades e aumento da eficiência de sistemas. Busca-se a obtenção de sistemas com morfologia e composição finamente controladas, com posterior avaliação das relações entre as características estruturais observadas e as propriedades ópticas e eletrônicas dos sólidos. O objetivo deste trabalho é a obtenção de novos materiais nanoetruturados contendo titânio e cério, com potencial absortividade na região do UV e/ou UV-Vis com a finalidade de empregá-los na fotocatálise de poluentes. Os óxidos de titânio contendo cério (0,5 50%) serão obtidos através da metodologia Sol-Gel com sistema em refluxo; e avaliados quanto suas propriedades estruturais (FTIR, Raman, XRD, BET e TGA), morfológicas (SEM) e ópticas (DRS no UV-Vis); além de realizar um estudo fotocatalítico da degradação de corantes quando submetidos a radiação solar (simulado) e na presença dos óxidos

The utilization of insoluble sources of micronutrients as concentrated suspensions (CSs) is increasing in Brazilian agriculture; however, much information regarding the physicochemical characterization of these products is required to demonstrate the absorption behavior by plant leaves. This study aimed to characterize the CSs available on the Brazilian market to support their potential use as foliar fertilizers. We selected five CSs containing Mn, five CSs containing Zn and three CSs containing Cu from five different companies. In each product, the mean particle size was evaluated by dynamic light scattering (DLS), the particle shape and size were evaluated by scanning electron microscopy (SEM), the aggregation degree was determined by the zeta potential and the heavy metal contents were determined by acid digestion followed by reading on ICP-OES. The mean hydrodynamic diameter of fertilizers containing Cu, Mn and Zn was 315 ± 55, 378 ± 184 and 435 ± 107 nm, respectively. The zeta potential varied from –20 to –30 mV, indicating potential particle aggregation and formation of higher structures. SEM images indicated great variation in the size and shape of the particles in each product. All products exhibited concentrations of toxic elements within the legislation thresholds. The average particle size of CSs currently marketable in Brazil does not allow their classification as nanomaterials (< 100 nm). Therefore, their foliar absorption is unlikely, once the particle size is higher than the exclusion limit observed for stomata and cuticle pathways, as well as the nutrient content as ions is low according to the solubility constant.

Several metallic nanomaterials (NMs), such as titanium dioxide nanomaterials (TiO2), present beneficial properties with a broad range of innovative applications. The human population is exposed to TiO2, particularly by ingestion, due to its increasing use as a food additive and inclusion in dietary supplements and food packaging materials. Whether this oral exposure may lead to adverse local or systemic outcomes has been the subject of research, but studies have generated contradictory results, reflecting differences in the physicochemical properties of the TiO2 studied, effects of the surrounding matrix, and modifications during digestion. This work aimed to investigate the toxic effects of three different TiO2 NMs (NM-103, NM-103 and NM-105) on the gastrointestinal tract cells, Caco-2 and HT29-MTX-E12, after the use of the standardized static INFOGEST 2.0 in vitro digestion method to mimic human digestion of TiO2, contributing to hazard assessment. The results show that, for one of the digested TiO2 NMs studied (NM-105), a more pronounced toxicity occurs after exposure of HT29-MTX-E12 intestinal cells, as compared to undigested NM, concomitantly with subtle changes in characteristics of the NM. Thus, the inclusion of the digestion simulation in the safety evaluation of ingested NMs through in vitro bioassays can better integrate the modifications that NMs suffer in the organism. It is expected that such an approach will reduce uncertainties in the hazard assessment of ingested NMs for human health.

The effects of several copper (Cu) and silver (Ag) nanomaterials were assessed using the cellular energy allocation (CEA), a methodology used to evaluate the energetic status and which relates with organisms’ overall condition and response to toxic stress. Enchytraeus crypticus (Oligochatea), was exposed to the reproduction effect concentrations EC20/50 of several Cu and Ag materials (CuNO3, Cu-Field, Cu-Nwires and Cu-NPs; AgNO3, Ag NM300K, Ag-NPs Non-coated and Ag-NPs PVP-coated) for 7 days (0-3-7d). The parameters measured were the total energy reserves available (protein, carbohydrate and lipid budgets) and the energy consumption (Ec) integrated to obtain the CEA. Results showed that these parameters allowed a clear discrimination between Cu and Ag, but less clearly within each of the various materials. For Cu there was an increase in Ec and protein budget, while for Ag a decrease was observed. The results corroborate known mechanisms, e.g., with Cu causing an increase in metabolic rate whereas Ag induces mitochondrial damage. The various Cu forms seem to activate different mechanisms with size and shape (e.g., Cu-NPs versus Cu-Nwires), causing clearly different effects. For Ag, results are in line with a slower oxidation rate of Ag-NMs in comparison with Ag-salt and hence delayed effects.

The encapsulation of antifouling compounds, such as DCOIT (4,5-Dichloro-2-octylisothiazol- 3(2H)-one), in mesoporous silica nanocapsules (SiNC) has recently been demonstrated to be an eco-friendly alternative to decrease biocide toxicity towards marine non-target species. However, the lack of information on the chronic effects of such nanomaterials on non-target tropical species is critical for a more comprehensive environmental risk assessment. Thus, the present study aimed to assess the chronic toxicity and hazard of the soluble and encapsulated forms of DCOIT on neotropical marine species. Chronic tests were conducted with six ecologically relevant species. No effect concentration (NOEC) values were combined with NOEC values reported for tropical species to assess the hazard using the probabilistic approach to derive each predicted no effect concentration (PNEC). The SiNC-DCOIT was three- to ten-fold less toxic than soluble DCOIT. Probabilistic-based PNECs were set at 0.0001 and 0.0097 g DCOIT L1 for the biocide soluble and nanostructured forms, respectively. The immobilization of DCOIT into SiNC led to an 84-fold hazard decrease, confirming that the encapsulation of DCOIT into SiNC is a promising eco-friendly alternative technique, even in a chronic exposure scenario. Therefore, the present study will contribute to better management of the environmental risk of such innovative products in the tropical marine environment.

Several metallic nanomaterials (NMs), such as titanium dioxide nanomaterials (TiO2), present beneficial properties with a broad range of innovative applications. The human population is exposed to TiO2, particularly by ingestion, due to its increasing use as a food additive and inclusion in dietary supplements and food packaging materials. Whether this oral exposure may lead to adverse local or systemic outcomes has been the subject of research, but studies have generated contradictory results, reflecting differences in the physicochemical properties of the TiO2 studied, effects of the surrounding matrix, and modifications during digestion. This work aimed to investigate the toxic effects of three different TiO2 NMs (NM-103, NM-103 and NM-105) on the gastrointestinal tract cells, Caco-2 and HT29-MTX-E12, after the use of the standardized static INFOGEST 2.0 in vitro digestion method to mimic human digestion of TiO2, contributing to hazard assessment. The results show that, for one of the digested TiO2 NMs studied (NM-105), a more pronounced toxicity occurs after exposure of HT29-MTX-E12 intestinal cells, as compared to undigested NM, concomitantly with subtle changes in characteristics of the NM. Thus, the inclusion of the digestion simulation in the safety evaluation of ingested NMs through in vitro bioassays can better integrate the modifications that NMs suffer in the organism. It is expected that such an approach will reduce uncertainties in the hazard assessment of ingested NMs for human health.

The existence of a selective blood-brain barrier (BBB) and neurovascular coupling are two unique central nervous system vasculature features that result in an intimate relationship between neurons, glia, and blood vessels. This leads to a significant pathophysiological overlap between neurodegenerative and cerebrovascular diseases. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease whose pathogenesis is still to be unveiled but has mostly been explored under the light of the amyloid-cascade hypothesis. Either as a trigger, bystander, or consequence of neurodegeneration, vascular dysfunction is an early component of the pathological conundrum of AD. The anatomical and functional substrate of this neurovascular degeneration is the BBB, a dynamic and semi-permeable interface between blood and the central nervous system that has consistently been shown to be defective. Several molecular and genetic changes have been demonstrated to mediate vascular dysfunction and BBB disruption in AD. The isoform ε4 of Apolipoprotein E is at the same time the strongest genetic risk factor for AD and a known promoter of BBB dysfunction. Low-density lipoprotein receptor-related protein 1 (LRP-1), P-glycoprotein, and receptor for advanced glycation end products (RAGE) are examples of BBB transporters implicated in its pathogenesis due to their role in the trafficking of amyloid-β. This disease is currently devoid of strategies that change the natural course of this burdening illness. This unsuccess may partly be explained by our misunderstanding of the disease pathogenesis and our inability to develop drugs that are effectively delivered to the brain. BBB may represent a therapeutic opportunity as a target itself or as a therapeutic vehicle. In this review, we aim to explore the role of BBB in the pathogenesis of AD including the genetic background and detail how it can be targeted in future therapeutic research.

RNA-based medicines have distinct advantages in comparison to conventional drug such as small molecules or other biomolecules in terms of specificity, potency, number of accessible targets, manufacturing, among others. However, several obstacles need to be addressed before the clinical translation of RNA-based therapeutics such as targeting and intracellular delivery. The main objective of this thesis was the development of biocompatible light-triggerable nanoparticle libraries to improve cell targeting and intracellular delivery of RNA-based medicines, for both in vitro and in vivo applications. The two nanoparticle libraries (each one of them were obtained from poly(amido amine) polymers) were synthesized by high-throughput strategies via Michael-type addition. In one of the libraries (160 NP formulations), the polymers were sensitive to light because they incorporated in their backbone a photo-cleavable linker (PCL) while, in the other (110 NP formulations), the polymer backbone was not sensitive to light but was modified with a pendent photo-cleavable molecule. In both cases, the polymers were precipitated in aqueous solution to form nanoparticles which were then complexed with siRNA or miRNA molecules. NP dissociate at different rates once activated by UV or a blue laser. A significant number of NPs showed more than 75% decrease in concentration after 10 min of light activation. In a High Content Screening, the NP library was screened for a fast transfecting carrier (with less than one hour of cell-material contact) in a model system (anti-GFP siRNA), that cause higher gene silencing than a commercial agent with boosted efficacy using light activation. More than a third of light-triggered NPs was found with increased gene silencing efficacy (up to 500%) in comparison to commercial transfection agent (Lipofectamine RNAiMAX) without compromised cell viability. Several candidates were further characterised in secondary tests regarding their specificity to skin cells (with some NPs that were more internalised by a specific type of cell than others) and endolysosomal escape. Functional studies before and after light activation with therapeutic relevant siRNA and miRNA prove applicability of the carriers for in vivo experimentation. Moreover, we have confirmed the advantages of one of the candidate formulations in a wound healing animal model, for the delivery of a recently identified skin regenerative miRNA. This thesis describes a powerful platform with the first light-activatable nanoparticle library with remote activation and efficient in vivo non-coding RNA delivery in wound healing. The results presented here are an exciting first step towards the translation of light-triggerable polymeric carriers for RNA-based therapeutics delivery.

Leishmaniasis is one of the deadliest neglected tropical diseases affecting 12-15 million people worldwide, especially in middle- and low-income countries. Rapid and accurate diagnosis of the disease is important for its adequate management and treatment. Several techniques are available for the diagnosis of leishmaniasis. Among these, parasitological and immunological tests are most widely used. However, in most cases, the utilized diagnostic techniques are not good enough, showing cross-reactivity and reduced accuracy. In recent years, many new methods have been reported with potential for improved diagnosis. This review focuses on the diagnosis of Leishmania exploring the biosensors and nanotechnology-based options for their detection. New developments including the use of nanomaterials as fluorophores, fluorescence quenchers as reducing agents and as dendrimers for signal improvement and amplification, together with the use of aptamers to replace antibodies are described. Future research opportunities to overcome the current limitations on the available diagnostic approaches are also discussed.

Microbial infections are still among the major public health concerns since several yeasts and fungi, and other pathogenic microorganisms, are responsible for continuous growth of infections and drug resistance against bacteria. Antimicrobial resistance rate is fostering the need to develop new strategies against drug-resistant superbugs. Antimicrobial peptides (AMPs) are small peptide-based molecules of 5-100 amino acids in length, with potent and broad-spectrum antimicrobial properties. They are part of the innate immune system, which can represent a minimal risk of resistance development. These characteristics contribute to the description of these molecules as promising new molecules in the development of new antimicrobial drugs. However, efforts in developing new medicines have not resulted in any decrease of drug resistance yet. Thus, a technological approach on improving existing drugs is gaining special interest. Nanomedicine provides easy access to innovative carriers, which ultimately enable the design and development of targeted delivery systems of the most efficient drugs with increased efficacy and reduced toxicity. Based on performance, successful experiments, and considerable market prospects, nanotechnology will undoubtedly lead a breakthrough in biomedical field also for infectious diseases, as there are several nanotechnological approaches that exhibit important roles in restoring antibiotic activity against resistant bacteria.