Introduction: Research on gold nanoparticles (AuNPs) occupies a prominent place in the field of biomedicine nowadays, being their putative toxicity and bioactivity areas of major concern. The green synthesis of metallic nanoparticles using extracts from marine organisms allows the avoidance of hazardous production steps while maintaining features of interest, thus enabling the exploitation of their promising bioactivity. Objective: To synthesize and characterize AuNPs using, for the first time, macroalga Cystoseira tamariscifolia aqueous extract ([email protected]). Methods: Algal aqueous extracts were used for the synthesis of AuNPs, which were characterized using a wide panel of physicochemical techniques and biological assays. Results: The characterization by UV-Vis spectroscopy, transmission electron microscopy, Z-potential and infrared spectroscopy confirmed that [email protected] were stable, spherical and polycrystalline, with a mean diameter of 7.6 ± 2.2 nm. The antioxidant capacity of the extract, prior to and after synthesis, was analyzed in vitro, showing that the high antioxidant potential was not lost during the synthesis. Subsequently, in vitro and in vivo toxicity was screened, by comparing two species of the genus Cystoseira (C. tamariscifolia and C. baccata) and the corresponding biosynthesized gold nanoparticles ([email protected] and [email protected]). Cytotoxicity was tested in mouse (L929) and human (BJ5ta) fibroblast cell lines. In both cases, only the highest (nominal) test concentration of both extracts (31.25 mg/mL) or [email protected] (12.5 mM) significantly affected cell viability, as measured by the MTT assay. These results were corroborated by a Fish Embryo Acute Toxicity (FET) test. Briefly, it was shown that, at the highest (nominal) tested concentration (31.25 mg/mL), CT extract induced significantly higher cytotoxicity and embryotoxicity than CB extract. However, it was demonstrated that [email protected], but not [email protected], were generally non-toxic. At sub-lethal (nominal) test concentrations (1.25 and 2.5 mM), [email protected] affected zebrafish embryonic development to a much lesser extent than [email protected] In vitro wound healing assays also revealed that, while other experimental conditions did not impact cell migration, CT and [email protected] displayed a moderate positive effect. Conclusion: [email protected] and [email protected] display promising features, desirable for biomedical applications, as wound healing.

Around 200 cytokines with roles in cell signaling have been identified and studied, with the vast majority belonging to the four-α-helix bundle family. These proteins exert their function by binding to specific receptors and are implicated in many diseases. The use of several cytokines as therapeutic targets has been approved by the FDA, however their rapid clearance in vivo still greatly limits their efficacy. Nano-based drug delivery systems have been widely applied in nanomedicine to develop safe, specific and controlled delivery techniques. Nevertheless, each nanomaterial has its own specifications and their suitability towards the biochemical and biophysical properties of the selected drug needs to be determined, weighing in the final choice of the ideal nano drug delivery system. Nanoparticles remain the most used vehicle for cytokine delivery, where polymeric carriers represent the vast majority of the studied systems. Liposomes and gold or silica nanoparticles are also explored and discussed in this review. Additionally, surface functionalization is of great importance to facilitate the attachment of a wide variety of molecules and modify features such as bioavailability. Since the monitoring of cytokine levels has an important role in early clinical diagnosis and for assessing therapeutic efficacy, nanotechnological advances are also valuable for nanosensor development.

The possibility of using the RNA interference (RNAi) mechanisms in gene therapy was one of the scientific breakthroughs of the last century. Despite the extraordinary therapeutic potential of this approach, the need for an efficient gene carrier is hampering the translation of the RNAi technology to the clinical setting. Although a diversity of nanocarriers has been described, liposomes continue to be one of the most attractive siRNA vehicles due to their relatively low toxicity, facilitated siRNA complexation, high transfection efficiency and enhanced pharmacokinetic properties. This review focuses on RNAi as a therapeutic approach, the challenges to its application, namely the nucleic acids’ delivery process, and current strategies to improve therapeutic efficacy. Additionally, lipid-based nanocarriers are described, and lessons learned from the relation between biophysical properties and biological performance of the dioctadecyldimethylammonium:monoolein (DODAX: MO) system are explored. Liposomes show great potential as siRNA delivery systems, being safe nanocarriers to protect nucleic acids in circulation, extend their half-life time, target specific cells and reduce off-target effects. Nevertheless, several issues related to delivery must be overcome before RNAi therapies reach their full potential, namely target-cell specificity and endosomal escape. Understanding the relationship between biophysical properties and biological performance is an essential step in the gene therapy field.

In the last decades, marine macroalgae have drawn attention mainly because of their bioactive constituents. Most brown algae are distributed over coastal areas of the Atlantic Ocean, Mediterranean Sea, Aegean Sea and Black Sea, and their composition varies with endogenous and exogenous factors. Phlorotannins, fatty acids, sterols and carbohydrates are some of the compounds responsible for biological activities related to cytotoxic, antiviral, antifungal, antibacterial, antidiabetic, antioxidant and anti-inflammatory potential. In this review we seek to highlight some of the compounds responsible for these last two biological activities, which have enormous importance for the management of neurodegenerative diseases, such as Alzheimer and Parkinson’s, with neuroinflammation and oxidative stress as hallmarks. However, one of the major problems associated with treating these diseases is the highly selective blood-brain-barrier, which can be overcome with nanocarriers used as delivery systems. Weighing the risks, benefits and toxicity of the used nanoparticles is nevertheless important. We also discuss zebrafish as an upcoming adequate biological model for in vivo screening of risks and benefits of such treatment strategies. This review aims to enable researchers working in the exploitation of these macroalgae and in the use of nanocarriers to potentiate the controlled delivery of bioactive compounds.

Oncostatin M (OSM) and leukemia inhibitory factor (LIF) are pleiotropic cytokines from the interkeukine-6 family, associated with several disorders, and present significant potential in biomedicine. However, their therapeutic use is highly constrained by factors such as short circulating half-life and narrow therapeutic window. The conjugation of cytokines with elastin-like recombinamers (ELR) holds the potential to circumvent these limitations due to the ability of self-assembling upon a thermal stimulus, remarkable biocompatibility, and ease of processing. In this work, we report on the development of genetically engineered hybrid ELR conjugates by fusing the DNA sequences coding for murine/human OSM and LIF into the C-terminus of an ELR. The resulting hybrid fusion proteins demonstrated to retain the thermal properties of the ELR, which enabled the nonchromatographic purification by employing simple hot/cold cycles. Nanoparticles and free-standing films were obtained by self-assembly and solvent casting, respectively, using environmentally friendly processes (mild conditions and water-based methods). Both materials were characterized for their properties, revealing the absence of hemotoxicity upon contact with red blood cells and promising features for potential therapeutic applications. Overall, this work represents a step forward in the development of advanced functionalized biomaterials suitable for localized cytokine therapy.

The marine ecosystem has captured a major attention in recent years since various biologically active compounds have been isolated and screened for pharmacological activity from dissimilar marine provenience. Marine biological resources can be considered an essential for nanotechnology, researchers had been interested to synthesize metallic nanoparticles from marine source because it is thought to be ecofriendly, nontoxic, environmentally acceptable ‘‘green procedures”, reduces the down-streaming process making it very cost effective and the availableness of the source from the diverse marine ecosystem becomes a much easier task. The biosynthesized nanoparticles from marine compound offer stabilized nanoparticles through compounds present in the marine source that make them more efficient for both biomedical and industrial applications[1]. In this regard, we have focus our attention in two algae of Cystoseira. It is a genus of marine brown macroalgae composed of about 40 species. It is widely distributed in the North East Atlantic, the Baltic Sea and the Mediterranean. This genus contains a wide variety of secondary metabolites (e.g. terpenoids, steroids, phlorotannins, phenolic compounds, carbohydrates, triacylglycerols/fatty acids, pigments, vitamins) that are associated with pharmacological properties, such as antioxidant, anti-inflammatory, cytotoxicity, anticancer, cholinesterase inhibition and anti-diabetic activities but also antibacterial, antifungal and anti-parasitic activities [2]. Cystoseira baccata (CB) and Cystoseira tamariscifolia (CT) are two species of this genus that differ in geographic distribution, morphology and possibly content of secondary metabolites. Gold nanoparticles are presently under intensive study since they can be the remarkable scaffold for novel biological and chemical applications owing to their unique electrical, chemical and optical properties. Such as their easy synthesis and good biocompatibility due to the low reactivity of the golden core. Therefore presenting potential applications in the development of new technologies in different fields such as in the food, cosmetic and pharmaceutical industry [3,4]. Previously, González-Ballesteros et al have reported the synthesis of gold nanoparticles with antitumor activity led by the macroalga CB [5]. In the present study, we have compared the ability of C. baccata and C. tamariscifolia (CT) in the synthesis of gold nanoparticles. With this aim, aqueous extracts of the two macroalgae were prepared and their reducing activity, total phenolic content and DPPH scavenging activity were determined before and after the synthesis of nanoparticles. Results showed that CT possess three times more reducing power, almost 4 times more phenolic content and 4 time more DPPH scavenging activity than CB. The nanoparticles obtained were characterized by UV-Vis spectroscopy and Transmission electron microscopy confirming the formation of spherical nanoparticles with a mean diameter of 8.4 ± 2.2 nm in the case of Au@CB and 7.6 ± 2.2 nm for Au@CT. In order to compare the biological potential of both CT and CB extracts and their respective gold nanoparticles (Au@CT and Au@CB), it was investigated whether they affect the viability in mouse (L929 cell line) and human (BJ5-ta cell line) fibroblast cells as in vitro models, by evaluating cellular metabolism by tetrazolium-based colorimetric cellular assay (MTT); cell membrane integrity by lactate dehydrogenase activity (LDH); wound-healing assay to asses effects on cell proliferation and migration capacity. Both algae extracts and derived nanoparticles present a non-cytotoxic profile in lower concentrations, which are efficient in cell regeneration, although with some differences between both species. For a correlation between in vitro and in vivo toxicity, the zebrafish embryo toxicity (ZET) assay, recomended by OECD to evaluate acute and chronic toxicity, was performed. This model organism has a translucent body, allowing real time observation, and allows the evaluation of whole organism responses, from mortality to more specific parameters such as neurotoxicity. The results show that toxicity is evident only at very high concentrations. These promising results thus support that green synthesis in CB and CT extracts of non-toxic, bioactive nanoparticles have an interesting potential for biomedical applications.