Valéria S. Marangoni

Cyto and genotoxicity of gold nanoparticles in human hepatocellular carcinoma and peripheral blood mononuclear cells.

Engineered nanomaterials have been extensively applied as active materials for technological applications. Since the impact of these nanomaterials on health and environment remains undefined, research on their possible toxic effects has attracted considerable attention. It is known that in humans, for example, the primary site of gold nanoparticles (AuNps) accumulation is the liver. The latter has motivated research regarding the use of AuNps for cancer therapy, since specific organs can be target upon appropriate functionalization of specific nanoparticles. In this study, we investigate the geno and cytotoxicity of two types of AuNps against human hepatocellular carcinoma cells (HepG2) and peripheral blood mononuclear cells (PBMC) from healthy human volunteers. The cells were incubated in the presence of different concentrations of AuNps capped with either sodium citrate or polyamidoamine dendrimers (PAMAM). Our results suggest that both types of AuNps interact with HepG2 cells and PBMC and may exhibit in vitro geno and cytotoxicity even at very low concentrations. In addition, the PBMC were less sensitive to DNA damage toxicity effects than cancer HepG2 cells upon exposure to AuNps.

Synthesis and characterization of jacalin-gold nanoparticles conjugates as specific markers for cancer cells.

New nanobiocomposites that combine nanoparticles and biomolecules have been shown very relevant for medical applications. Recently, cancer diagnostics and treatment have benefited from the development of nanobiocomposites, in which metallic or magnetic nanoparticles are conjugated with specific biomolecules for selective cell uptake. Despite recent advances in this area, the biomedical applications of these materials are still limited by the low efficiency of functionalization, low stability, among other factors. In this study, we report the synthesis of jacalin-conjugated gold nanoparticles, a nanoconjugate with potential application in medical areas, especially for cancer diagnosis. Jacalin is a lectin protein and it was employed due to its ability to recognize the Galβ1-3GalNAc disaccharide, which is highly expressed in tumor cells. Gold nanoparticles (AuNPs) were synthesized in the presence of generation 4 polyamidoamine dendrimer (PAMAM G4) and conjugated with fluorescein isothiocyanate (FITC)-labeled jacalin. The AuNPs/jacalin nanoconjugates were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and vibrational spectroscopy (FTIR). We also performed an investigation using isothermal titration calorimetry (ITC) and fluorescence quenching measurements to understand the interactions occurring between the AuNPs and jacalin, which revealed that the nanoconjugate formation is driven by an entropic process with good affinity. Furthermore, in vitro tests revealed that the AuNPs/jacalin-FITC nanoconjugates exhibited higher affinity for leukemic K562 cells than for healthy mononuclear blood cells, which could be useful for biomedical applications, including cancer cells imaging.

Structural characterization of emeraldine-salt polyaniline/gold nanoparticles complexes

Gold nanoparticles (Au NPs) stabilized with polyamidoamine dendrimers (Au-PAMAM) or sodium citrate (Au-CITRATE) were synthesized and complexed with polyaniline emeraldine-salt form (ES-PANI). The complexes were characterized using structural and morphological techniques, including X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Zeta Potential analyses, and Fourier-Transformed Infrared spectroscopy (FTIR). When the Au-CITRATE NPs are added to the polymeric solution, the formation of a precipitate is clearly observed. The precipitate exhibited a different morphology from that found for ES-PANI and Au-CITRATE NPs, suggesting the formation of ES-PANI coating over the surface of Au-CITRATE NPs. On the other hand, when the Au-PAMAM NPs are incorporated into the ES-PANI solution, none interaction was observed, probably due to the repulsive electrostatic interactions, being the organization of the ES-PANI chains unaffected by the presence of the Au-PAMAM NPs.

A Detailed Investigation on the Interactions between Magnetic Nanoparticles and Cell Membrane Models

The understanding of the interactions between small molecules and magnetic nanoparticles is of great importance for many areas of bioapplications. Although a large array of studies in this area have been performed, aspects involving the interaction of magnetic nanoparticles with phospholipids monolayers, which can better mimic biological membranes, have not yet been clarified. This study was aimed at investigating the interactions between Langmuir films of dipalmitoyl phosphatidylglycerol and dipalmitoyl phosphatidylcholine, obtained on an aqueous subphase, and magnetic nanoparticles. Sum-frequency generation (SFG) vibrational spectroscopy was used to verify the orientation and molecular conformation and to better understand the interactions between phospholipids and the magnetic nanoparticles. Surface pressure-area isotherms and SFG spectroscopy made it possible to investigate the interaction of these nanomaterials with components of phospholipids membranes at the water surface.

Nanotecnologia em medicina: aspectos fundamentais e principais preocupações

#NANOTECHNOLOGY IN MEDICINE: CONCEPTS AND CONCERNS. The recent advances in the development of nanomaterials have opened new and exciting opportunities for their applications in medicine. These applications include molecular imaging, drug-delivery, and photothermal therapy. Despite the progress in medicinal applications of nanomaterials, several key problems remain unaddressed. Recent advances in this area include the enhancement of sensitivity in early diagnosis and therapy, in addition to investigations into the possible toxicity of nanomaterials. However, since little is known about the toxicity of nanomaterials, the regulation of these materials is a slow and complex process. This paper reviews the current scenario in the applications of nanomaterials in medicine as well as the main concerns and regulatory questions.

Differences in the Aspect Ratio of Gold Nanorods that Induce Defects in Cell Membrane Models

Understanding the interactions between biomolecules and nanomaterials is of great importance for many areas of nanomedicine and bioapplications. Although studies in this area have been performed, the interactions between cell membranes and nanoparticles are not fully understood. Here, we investigate the interactions that occur between the Langmuir monolayers of dipalmitoylphosphatidyl glycerol (DPPG) and dipalmitoylphosphatidyl choline (DPPC) with gold nanorods (NR)-with three aspect ratios-and gold nanoparticles. Our results showed that the aspect ratio of the NRs influenced the interactions with both monolayers, which suggest that the physical morphology and electrostatic forces govern the interactions in the DPPG-NR system, whereas the van der Waals interactions are predominant in the DPPC-NR systems. Size influences the expansion isotherms in both systems, but the lipid tails remain conformationally ordered upon expansion, which suggests phase separation between the lipids and nanomaterials at the interface. The coexistence of lipid and NP regions affects the elasticity of the monolayer. When there is coexistence between two phases, the elasticity does not reflect the lipid packaging state but depends on the elasticity of the NP islands. Therefore, the results corroborate that nanomaterials influence the packing and the phase behavior of the mimetic cell membranes. For this reason, developing a methodology to understand the membrane-nanomaterial interactions is of great importance.

Synthesis, characterization and application of Ag doped ZnO nanoparticles in a composite resin

The biofilm accumulation over the composite resin restorations can contribute to the formation of secondary caries. In this way, antibacterial restorative composite resins are highly desired. Then, the purpose of this study was to modify a composite resins using Ag doped ZnO nanoparticles (NPs), evaluate the antibacterial and mechanical properties of the modified composite resin. The ZnO/AgNPs were synthesized by two different routes, polymeric precursor and coprecipitation methods, and characterized by thermal decomposition, X-ray diffraction, specific surface area by N2 desorption/desorption and scanning electron microscopy (SEM). Antibacterial activity of composite resin specimens (4 mm in height and 2 mm in diameter; n = 15) modified by ZnO/Ag nanoparticles was performed against 7-days Streptococcus mutans biofilm. Colony forming units (CFU/mL) were used to evaluate the bacterial activity. Additionally, the morphology and the bacteria adherence area were analyzed by SEM images. Cylindrical specimens (6 mm in height and 4 mm in diameter; n = 20) of the composite resin containing ZnO/Ag NPs were prepared to perform compressive strength in a universal mechanical test machine, and the surface of fractured specimens was analyzed by EDX element mapping to verify NPs homogeneity. The normal distribution was confirmed and the two-way analysis of variance (ANOVA) and Tukeys test for pair comparison were performed. The nanospheres of ZnO/Ag lead to a better biofilm inhibition, than nanoplates. No difference on compressive strength was found for the composite resin modified by ZnO/Ag nanoplates. Based on these results, this material could be a good option as a new restorative material.

Synthesis and characterization of PLGA nanoparticles containing mixture of curcuminoids for optimization of photodynamic inactivation

Because of excessive use of antibiotics there is a growth in the number of resistant strains. Due to this growth of multiresistant bacteria, the number of searches looking for alternatives antibacterial therapeutic has increased, and among them is the antimicrobial photodynamic therapy (aPDT) or photodynamic inactivation (PDI). The photodynamic inactivation involves the action of a photosensitizer (PS), activated by a specific wavelength, in the present of oxygen, resulting in cytotoxic effect. Natural curcumin, consists of a mixture of three curcuminoids: curcumin, demethoxycurcumin and bis-demethoxycurcumin. Curcumin has various pharmacological properties, however, has extremely low solubility in aqueous solutions, which difficult the use as therapeutic agent. The present study aims to develop polymeric PLGA nanoparticles containing curcuminoids to improve water solubility, increase bioavailability providing protection from degradation (chemistry and physics), and to verify the efficacy in photodynamic inactivation of microorganisms. The PLGA-CURC were synthesized by nanoprecipitation, resulting in two different systems, with an average size of 172 nm and 70% encapsulation efficiency for PLGA-CURC1, and 215 nm and 80% for PLGA-CURC2. Stability tests showed the polymer protected the curcuminoids against premature degradation. Microbiological tests in vitro with curcuminoids water solution and both suspension of PLGA-CURC were efficient in Gram-positive bacterium and fungus. However, the solution presented dark toxicity at high concentrations, unlike the nanoparticles. Thus, it was concluded that it was possible to let curcuminoids water soluble by encapsulation in PLGA nanoparticles, to ensure improved stability in aqueous medium (storage), and to inactivate bacteria and fungus.