Cytotoxicity of mini gold nanorods: intersection with extracellular vesicles.

It is well-known that there are size- and shape-dependencies to nanoparticle uptake and processing by living cells. Small gold nanorods have shown to exhibit low toxicity and high clearance rates when compared to larger ones, making smaller particles more desirable for biomedical applications. In this study gold mini-rods (approximately 9.5 × 23, 8 × 26, and 6 × 26 nm, corresponding to aspect ratios 2.5, 3.2 and 4.1) and gold nanospheres (15.6 nm average diameter) were synthesized, and wrapped with cationic and anionic polyelectrolytes. This library of colloidally stable nanomaterials was exposed to human dermal fibroblasts at the relatively low concentration of 1 nM for each nanoparticle type. The cytotoxic profile of these nanoparticles and their influence on the small extracellular vesicles released by the cells was assessed. It was observed that although the nanoparticles were found in vesicles inside the cells, the cell viability, the mitochondrial membrane potential and levels of reactive oxygen species were not markedly affected by the mini gold nanorods. The production of extracellular vesicles by the cells was unaffected by gold nanoparticle exposure; moreover, no gold nanoparticles were observed in extracellular vesicles in the exosomal size range. Taken together, these results suggest that these mini gold nanorods are suitable for a wide range of cellular applications for relatively short-term studies.

Biocompatible gum arabic-gold nanorod composite as an effective therapy for mistreated melanomas.

Advanced melanoma patients that are not included in common genetic classificatory groups lack effective and safe therapeutic options. Chemotherapy and immunotherapy show unsatisfactory results and devastating adverse effects for these called triple wild-type patients. New approaches exploring the intrinsic antitumor properties of gold nanoparticles might reverse this scenario as a safer and more effective alternative. Therefore, we investigated the efficacy and safety of a composite made of gum arabic-functionalized gold nanorods (GA-AuNRs) against triple wild-type melanoma. The natural polymer gum arabic successfully stabilized the nanorods in the biological environment and was essential to improve their biocompatibility. In vivo results obtained from treating triple wild-type melanoma-bearing mice showed that GA-AuNRs remarkably reduced primary tumor growth by 45%. Furthermore, GA-AuNRs induced tumor histological features associated with better prognosis while also reducing superficial lung metastasis depth and the incidence of intrapulmonary metastasis. GA-AuNRs' efficacy comes from their capacity to reduce melanoma cells ability to invade the extracellular matrix and grow into colonies, in addition to a likely immunomodulatory effect induced by gum arabic. Additionally, a broad safety investigation found no evidence of adverse effects after GA-AuNRs treatment. Therefore, this study unprecedentedly reports GA-AuNRs as a potential nanomedicine for advanced triple wild-type melanomas.

Impact of environmental mercury exposure on the blood cells oxidative status of fishermen living around Mundaú lagoon in Maceió - Alagoas (AL), Brazil.

Mercury in the aquatic environment can lead to exposure of the human population and is a known toxic metal due to its capacity for accumulation in organs. We aimed to evaluate the mercury level in the blood and urine of fishermen and correlate it with the level of oxidative stress in blood cells. We show in this case-control study that the fishermen of the exposed group (case) of Mundaú Lagoon (Maceió - Alagoas, Brazil) have higher concentrations of total mercury in the blood (0.73-48.38 µg L-1) and urine (0.430-10.2 µg L-1) than the total mercury concentrations in blood (0.29-17.30 µg L-1) and urine (0.210-2.65 µg L-1) of the control group. In the blood cells of fishermen, we observed that the lymphomononuclear cells produced high levels of reactive oxygen species (61.7%), and the erythrocytes presented increased lipid peroxidation (151%) and protein oxidation (41.0%) and a decrease in total thiol (36.5%), GSH and the REDOX state (16.5%). The activity of antioxidant system enzymes (SOD, GPx, and GST) was also reduced in the exposed group by 26.9%, 28.3%, and 19.0%, respectively. Furthermore, hemoglobin oxygen uptake was decreased in the exposed group (40.0%), and the membrane of cells presented increased osmotic fragility (154%) compared to those in the control group. These results suggest that mercury in the blood of fishermen can be responsible for causing impairments in the oxidative status of blood cells and is probably the cause of the reduction in oxygen uptake capacity and damage to the membranes of erythrocytes.

Antioxidant and antimicrobial activity of red propolis embedded mesoporous silica nanoparticles.

This work brings the promise of MCM-41 mesoporous silica as a vehicle for red propolis for the development of controlled release drugs and delivery to a specific target site. The synthesis of MCM-41 by the sol-gel method with a pore size of approximately 3.6 nm and the incorporation of red propolis extract by the physical adsorption method in ethanolic medium were easily accomplished with around 15% encapsulation. MCM-41 and MCM-41 with red propolis (MCM-41/Pr) were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, thermal analysis, N2 adsorption-desorption, scanning electron microscopy, and an ultra-high-performance liquid chromatography-diode array detection (UPLC-DAD). In vitro release of encapsulated red propolis was analyzed in phosphate buffer at pH 7.2, 7.4, and 7.6. An in vitro test for MCM-41/Pr antioxidant activity was performed using 2,2-diphenyl-1-picrylhydrazyl as well as analysis of antibacterial activity against Staphylococcus aureus by the well diffusion method. UPLC-DAD analysis showed that the integrity of the red propolis constituents was maintained after the embed process, and the antioxidant and antibacterial activities were preserved.

Evaluation of gold nanorods toxicity on isolated mitochondria.

Gold nanorods (AuNRs) have been studied extensively in biomedicine due to their biocompatibility and their unique properties. Some studies reported that AuNRs selectively accumulate on cancer cell mitochondria causing its death. However, the immediate effects of this accumulation needed further investigations. In this context, we evaluated the effect of AuNRs on the mitochondrial integrity of isolated rat liver mitochondria. We verified that AuNRs decreased the mitochondrial respiratory ratio by decreasing the phosphorylation and maximal states. Additionally, AuNRs caused a decrease in the production of mitochondrial ROS and a delay in mitochondrial swelling. Moreover, even with cyclosporine A treatment, AuNRs disrupted the mitochondrial potential. With the highest concentration of AuNRs studied, disorganized mitochondrial crests and intermembrane separation were observed in TEM images. These results indicate that AuNRs can interact with mitochondria, disrupting the electron transport chain. This study provides new evidence of the immediate effects of AuNRs on mitochondrial bioenergetics.

Surface interactions of gold nanorods and polysaccharides: From clusters to individual nanoparticles.

Gold nanorods (AuNRs) are suitable for constructing self-assembled structures for the development of biosensing devices and are usually obtained in the presence of cetyltrimethylammonium bromide (CTAB). Here, a sulfated chitosan (ChiS) and gum arabic (GA) were employed to encapsulate CTAB/AuNRs with the purpose of studying the interactions of the polysaccharides with CTAB, which is cytotoxic and is responsible for the instability of nanoparticles in buffer solutions. The presence of a variety of functional groups such as the sulfate groups in ChiS and the carboxylic groups in GA, led to efficient interactions with CTAB/AuNRs as evidenced through UV-vis and FTIR spectroscopies. Electron microscopies (HR-SEM and TEM) revealed that nanoparticle clusters were formed in the GA-AuNRs sample, whereas individual AuNRs, surrounded by a dense layer of polysaccharides, were observed in the ChiS-AuNRs sample. Therefore, the presented work contributes to the understanding of the driving forces that control the surface interactions of the studied materials, providing useful information in the building-up of gold self-assembled nanostructures.

Palladium-benzodiazepine derivatives as promising metallodrugs for the development of antiepileptic therapies.

We synthesized two organometallic diazepam-palladium(II) derivatives by C-H activation of diazepam (DZP) with palladium salts, i.e., PdCl2 and Pd(OAc)2 (OAc=acetate). Both compounds obtained are air stable and were isolated in good yields. The anticonvulsant potential of the complexes, labeled [(DZP)PdCl]2 and [(DZP)PdOAc]2, was evaluated through two animal models: pentylenetetrazole (PTZ)- and picrotoxin (PTX)-induced convulsions. The organometallic DZP-palladium(II) acetate complex, [(DZP)PdOAc]2, significantly increased (p<0.01 or p<0.001) latencies and protected the animals against convulsions induced by PTZ and PTX, while the analogous chloro derivative, [(DZP)PdCl]2, was effective (p<0.01) only in the PTZ model. These effects appear to be mediated through the GABAergic system. The possible mechanism of action of the DZP-palladium(II) complexes was also confirmed with the use of flumazenil (FLU), a GABAA-benzodiazepine receptor complex site antagonist. Herein, we present the first report of the anticonvulsant properties of organometallic DZP-palladium(II) complexes as well as evidence that these compounds may play an important role in the study of new drugs to treat patients with epilepsy.