Core-shell Fe@Fex_xOy_y nanoring system: A versatile platform for biomedical applications

Iron oxide (maghemite and magnetite) nanoparticles are the most commonly used magnetic materials in nanomedicine because of their high biocompatibility. However, their low saturation magnetization (60–90 emu/g) limits their applicability. Here, we report a new core–shell (Fe@Fe$_x$O$_y$) nanoring system, which combines the high magnetic saturation of a metallic iron core (220 emu/g) and the biocompatibility of an iron oxide shell. To produce these nanostructures, hematite (α-Fe$_2$O$_3$) nanorings were annealed in a H$_2$ gas atmosphere for different periods to optimize the amount of metallic iron percentage (δ) in the system. Thus, nanostructures with different magnetic saturation (97 to 178 emu/g) could be obtained; based on their metallic iron content, these particles are labeled as Vortex Iron oxide Particle δ (VIPδ). Micromagnetic simulations confirmed that the VIPδ nanorings exhibit a vortex configuration, guaranteeing low remanence and coercitivity. Moreover, the system shows good biocompatibility in various assays as determined through cell viability measurements performed using two different human cell lines, which were exposed to VIP78% for 24 h. Therefore, VIPδ nanorings combine a magnetic vortex state and biocompatibility with their high magnetic saturation and can thus serve as a platform that can be tuned during the synthesis based on desired biomedical application

Nanomicelles of Radium Dichloride [223Ra]RaCl2 Co-Loaded with Radioactive Gold [198Au]Au Nanoparticles for Targeted Alpha–Beta Radionuclide Therapy of Osteosarcoma

Alpha and beta particulate radiation are used for non-treated neoplasia, due to their ability to reach and remain in tumor sites. Radium-223 (223Ra), an alpha emitter, promotes localized cytotoxic effects, while radioactive gold (198Au), beta-type energy, reduces radiation in the surrounding tissues. Nanotechnology, including several radioactive nanoparticles, can be safely and effectively used in cancer treatment. In this context, this study aims to analyze the antitumoral effects of [223Ra]Ra nanomicelles co-loaded with radioactive gold nanoparticles ([198Au]AuNPs). For this, we synthesize and characterize nanomicelles, as well as analyze some parameters, such as particle size, radioactivity emission, dynamic light scattering, and microscopic atomic force. [223Ra]Ra nanomicelles co-loaded with [198Au]AuNPs, with simultaneous alpha and beta emission, showed no instability, a mean particle size of 296 nm, and a PDI of 0.201 (±0.096). Furthermore, nanomicelles were tested in an in vitro cytotoxicity assay. We observed a significant increase in tumor cell death using combined alpha and beta therapy in the same formulation, compared with these components used alone. Together, these results show, for the first time, an efficient association between alpha and beta therapies, which could become a promising tool in the control of tumor progression

Multidisciplinary studies of ancient calcified tissues: renal stones from mummies

The renal stones found in the mummies of Pandolfo III Malatesta, Lord of Fano (1370–1427) and an anonymous nobleman from Popoli (XVIII century) were investigated using different techniques. Both specimens were examined with binocular stereomicroscopy (BSM) and scanning electron microscopy (SEM), also with energy dispersive X-ray analysis (EDX). Multiple tiny fragments from surface and inner portions were submitted to X-ray diffraction (XRD) analysis. Subsequently, the calculi were imaged with microcomputed tomography (micro CT).The stone from Pandolfo had a mulberry-like surface with honey brown colour and measured 12 mm in largest diameter. Along with the organic constituents (C, O, and N), the following chemical elements were detected: K, S, Si, Cl, Ca, P, Na, and Ba. The calculus was composed of ammonium acid urate (95%) and calcium oxalate dihydrate (weddellite) (5%). Internal structure consisted of aggregated large spheroidal crystals with different density values. In the case from Popoli, the ovoidal mass with small superficial spherical buds measured 22×16×15 mm. The cut surface showed a central nucleus of sharp-edged crystals and concentric laminations. Detected chemical elements were: C, O, N,Ca, P, K, S, Cl, and Na. The stone composition was calcium oxalate monohydrate (whewellite; 90%) and calcium phosphate (hydroxylapatite; 10%). Internal structure detail revealed concentric laminations and aggregates of similar density values. These observations enabled us to propose an ideal protocol for the examination of stones that can be found in mummies and in osteoarcheological material. After preliminary observation with BSM, the specimen should be imaged with microCT, in order to trace a detailed map of the external surface and the whole calculus and guide the following SEM-EDX measurements for elemental distribution analysis. Matching the results from these methods avoids destructive XRD analysis and may allow to obtain an affordable evaluation of chemical composition on the entire stone, following a conservative approach

Cellular behavior as a dynamic field for exploring bone bioengineering: A closer look at cell-biomaterial interface

Bone is a highly dynamic and specialized tissue, capable of regenerating itself spontaneously when afflicted by minor injuries. Nevertheless, when major lesions occur, it becomes necessary to use biomaterials, which are not only able to endure the cellular proliferation and migration, but also to substitute the original tissue or integrate itself to it. With the life expectancy growth, regenerative medicine has been gaining constant attention in the reconstructive field of dentistry and orthopedy. Focusing on broadening the therapeutic possibilities for the regeneration of injured organs, the development of biomaterials allied with the applicability of gene therapy and bone bioengineering has been receiving vast attention over the recent years. The progress of cellular and molecular biology techniques gave way to new-guided therapy possibilities. Supported by multidisciplinary activities, tissue engineering combines the interaction of physicists, chemists, biologists, engineers, biotechnologist, dentists and physicians with common goals: the search for materials that could promote and lead cell activity. A well-oriented combining of scaffolds, promoting factors, cells, together with gene therapy advances may open new avenues to bone healing in the near future. In this review, our target was to write a report bringing overall concepts on tissue bioengineering, with a special attention to decisive biological parameters for the development of biomaterials, as well as to discuss known intracellular signal transduction as a new manner to be explored within this field, aiming to predict in vitro the quality of the host cell/material and thus contributing with the development of regenerative medicine. (C) 2014 Elsevier Inc. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

The Effects of Titanium Dioxide Nanoparticles on Osteoblasts Mineralization: A Comparison between 2D and 3D Cell Culture Models

Although several studies assess the biological effects of micro and titanium dioxide nanoparticles (TiO2 NPs), the literature shows controversial results regarding their effect on bone cell behavior. Studies on the effects of nanoparticles on mammalian cells on two-dimensional (2D) cell cultures display several disadvantages, such as changes in cell morphology, function, and metabolism and fewer cell–cell contacts. This highlights the need to explore the effects of TiO2 NPs in more complex 3D environments, to better mimic the bone microenvironment. This study aims to compare the differentiation and mineralized matrix production of human osteoblasts SAOS-2 in a monolayer or 3D models after exposure to different concentrations of TiO2 NPs. Nanoparticles were characterized, and their internalization and effects on the SAOS-2 monolayer and 3D spheroid cells were evaluated with morphological analysis. The mineralization of human osteoblasts upon exposure to TiO2 NPs was evaluated by alizarin red staining, demonstrating a dose-dependent increase in mineralized matrix in human primary osteoblasts and SAOS-2 both in the monolayer and 3D models. Furthermore, our results reveal that, after high exposure to TiO2 NPs, the dose-dependent increase in the bone mineralized matrix in the 3D cells model is higher than in the 2D culture, showing a promising model to test the effect on bone osteointegration

Graphene and its derivatives: understanding the main chemical and medicinal chemistry roles for biomedical applications

Over the past few years, there has been a growing potential use of graphene and its derivatives in several biomedical areas, such as drug delivery systems, biosensors, and imaging systems, especially for having excellent optical, electronic, thermal, and mechanical properties. Therefore, nanomaterials in the graphene family have shown promising results in several areas of science. The different physicochemical properties of graphene and its derivatives guide its biocompatibility and toxicity. Hence, further studies to explain the interactions of these nanomaterials with biological systems are fundamental. This review has shown the applicability of the graphene family in several biomedical modalities, with particular attention for cancer therapy and diagnosis, as a potent theranostic. This ability is derivative from the considerable number of forms that the graphene family can assume. The graphene-based materials biodistribution profile, clearance, toxicity, and cytotoxicity, interacting with biological systems, are discussed here, focusing on its synthesis methodology, physicochemical properties, and production quality. Despite the growing increase in the bioavailability and toxicity studies of graphene and its derivatives, there is still much to be unveiled to develop safe and effective formulations

Nanomicelles of Radium Dichloride [223Ra]RaCl2 Co-Loaded with Radioactive Gold [198Au]Au Nanoparticles for Targeted Alpha–Beta Radionuclide Therapy of Osteosarcoma

Alpha and beta particulate radiation are used for non-treated neoplasia, due to their ability to reach and remain in tumor sites. Radium-223 (223Ra), an alpha emitter, promotes localized cytotoxic effects, while radioactive gold (198Au), beta-type energy, reduces radiation in the surrounding tissues. Nanotechnology, including several radioactive nanoparticles, can be safely and effectively used in cancer treatment. In this context, this study aims to analyze the antitumoral effects of [223Ra]Ra nanomicelles co-loaded with radioactive gold nanoparticles ([198Au]AuNPs). For this, we synthesize and characterize nanomicelles, as well as analyze some parameters, such as particle size, radioactivity emission, dynamic light scattering, and microscopic atomic force. [223Ra]Ra nanomicelles co-loaded with [198Au]AuNPs, with simultaneous alpha and beta emission, showed no instability, a mean particle size of 296 nm, and a PDI of 0.201 (±0.096). Furthermore, nanomicelles were tested in an in vitro cytotoxicity assay. We observed a significant increase in tumor cell death using combined alpha and beta therapy in the same formulation, compared with these components used alone. Together, these results show, for the first time, an efficient association between alpha and beta therapies, which could become a promising tool in the control of tumor progression