Novel Fe3O4 Nanoparticles with Bioactive Glass-Naproxen Coating: Synthesis, Characterization, and In Vitro Evaluation of Bioactivity.

Immune response to biomaterials, which is intimately related to their surface properties, can produce chronic inflammation and fibrosis, leading to implant failure. This study investigated the development of magnetic nanoparticles coated with silica and incorporating the anti-inflammatory drug naproxen, aimed at multifunctional biomedical applications. The synthesized nanoparticles were characterized using various techniques that confirmed the presence of magnetite and the formation of a silica-rich bioactive glass (BG) layer. In vitro studies demonstrated that the nanoparticles exhibited bioactive properties, forming an apatite surface layer when immersed in simulated body fluid, and biocompatibility with bone cells, with good viability and alkaline phosphatase activity. Naproxen, either free or encapsulated, reduced nitric oxide production, an inflammatory marker, while the BG coating alone did not show anti-inflammatory effects in this study. Overall, the magnetic nanoparticles coated with BG and naproxen showed promise for biomedical applications, especially anti-inflammatory activity in macrophages and in the bone field, due to their biocompatibility, bioactivity, and osteogenic potential.

Heating Capacity and Biocompatibility of Hybrid Nanoparticles for Magnetic Hyperthermia Treatment.

Cancer is one of the deadliest diseases worldwide and has been responsible for millions of deaths. However, developing a satisfactory smart multifunctional material combining different strategies to kill cancer cells poses a challenge. This work aims at filling this gap by developing a composite material for cancer treatment through hyperthermia and drug release. With this purpose, magnetic nanoparticles were coated with a polymer matrix consisting of poly (L-co-D,L lactic acid-co-trimethylene carbonate) and a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer. High-resolution transmission electron microscopy and selected area electron diffraction confirmed magnetite to be the only iron oxide in the sample. Cytotoxicity and heat release assays on the hybrid nanoparticles were performed here for the first time. The heat induction results indicate that these new magnetic hybrid nanoparticles are capable of increasing the temperature by more than 5 °C, the minimal temperature rise required for being effectively used in hyperthermia treatments. The biocompatibility assays conducted under different concentrations, in the presence and in the absence of an external alternating current magnetic field, did not reveal any cytotoxicity. Therefore, the overall results indicate that the investigated hybrid nanoparticles have a great potential to be used as carrier systems for cancer treatment by hyperthermia.

Equisetum hyemale-derived unprecedented bioactive composite for hard and soft tissues engineering.

Although Bioactive Glasses (BGs) have been progressively optimized, their preparation often still involves the use of toxic reagents and high calcination temperatures to remove organic solvents. In the present work, these synthesis related drawbacks were overcome by treating the ashes from the Equisetum hyemale plant in an ethanol/water solution to develop a bioactive composite [glass/carbon (BG-Carb)]. The BG-Carb was characterized by scanning electron microscopy, and transmission electron microscopy; and its chemical composition was assessed by inductively coupled plasma-optical emission spectroscopy. Brunauer-Emmett-Teller gas adsorption analysis showed a specific surface area of 121 m2 g-1. The formation of hydroxyapatite (HA) surface layer in vitro was confirmed by Fourier-transform infrared spectroscopy analysis before and after immersion in simulated body fluid (SBF) solution. The Rietveld refinement of the XRD patterns and selected area electron diffraction analyses confirmed HA in the sample even before immersing it in SBF solution. However, stronger evidences of the presence of HA were observed after immersion in SBF solution due to the surface mineralization. The BG-Carb samples showed no cytotoxicity on MC3T3-E1 cells and osteo-differentiation capacity similar to the positive control. Altogether, the BG-Carb material data reveals a promising plant waste-based candidate for hard and soft tissue engineering.

Long-term dexamethasone treatment increases the engraftment efficiency of human breast cancer cells in adult zebrafish.

The host immune system tends to reject xenogenic-implanted cells making tumor development in adult host animal models difficult. Immune system suppression is used for successful xenotransplantation of human cancer cells in many animal models. The studies of cancer development processes in vivo offer opportunities to understand cancer biology and discover new therapeutic strategies. In this context, zebrafish is a model that has been widely applied in the study of human diseases, such as cancer. However, the long-term immunosuppression of these adult zebrafish is still under study as a xenograft animal model for human cancer. This work aimed to evaluate the effects of 21 days of (long-term) exposure of dexamethasone in zebrafish-transplanted with MGSO-3 cells, human breast tumor cell line. Our results show that the animals, while kept on dexamethasone treatment, remained with a 50% reduction in the number of peripheral lymphocytes. In vitro data demonstrated that up to 7 days of dexamethasone treatment did not alter the morphology, proliferation, or viability of MGSO-3 cells. The animals that received a prolonged dexamethasone treatment allowed the engraftment of tumor cells in 100% of the zebrafish tested. These animals also showed tumor progression over 21 days. The experimental group that received only previous exposure to dexamethasone had their tumors regressed after 14 days. In conclusion, the prolonged use of dexamethasone in zebrafish showed a potential strategy for in vivo monitoring of xenograft tumor growth for development studies, as well as in anticancer drug discovery.

Koh group influence on titanium surfaces and pure sol-gel silica for enhanced osteogenic activity.

Although, the excellent level of success of titanium surfaces is based on the literature, there are some biological challenges such as unfavorable metabolic conditions or regions of poor bone quality where greater surface bioactivity is desired. Seeking better performance, we hypothesized that silica-based coating via sol-gel route with immersion in potassium hydroxide basic solution induces acceleration of bone mineralization. This in vitro experimental study coated titanium surfaces with bioactive glass synthesized by route sol-gel via hydrolysis and condensation of chemical alkoxide precursor, tetraethylorthosilicate (TEOS) and/or deposition of chemical compound potassium hydroxide (KOH) to accelerate bone apposition. The generated surfaces titanium(T), titanium with potassium hydroxide deposition (T + KOH), titanium with bioactive glass deposition synthesized by sol-gel route via tetraethylorthosilicate hydrolysis (TEOS), titanium with bioactive glass deposition synthesized by sol-gel route via tetraethylorthosilicate hydrolysis with potassium hydroxide deposition (TEOS + KOH) were characterized by 3D optical profilometry, scanning electron microscopy (SEM), transmission electron microscopy (TEM), contact angle by the sessile drop method, x-ray excited photoelectron spectroscopy (XPS) and energy dispersive x-ray spectrometer (EDX). The addition of the KOH group on the pure titanium (T) or bioactive glass (TEOS) surfaces generated a tendency for better results for mineralization. Groups covered with bioactive glass (TEOS, TEOS + KOH) tended to outperform even groups with titanium substrate (T, T + KOH). The addition of both, bioactive glass and KOH, in a single pure titanium substrate yielded the best results for the mineralization process.

Use of prebiotic carbohydrate as wall material on lime essential oil microparticles.

The aim of this work was to study the use of different prebiotic biopolymers in lime essential oil microencapsulation. Whey protein isolate, inulin and oligofructose biopolymers were used. The addition of prebiotic biopolymers reduced emulsion viscosity, although it produced larger droplet sizes (0.31-0.32 µm). Moisture values (2.94-3.13 g/100 g dry solids) and water activity (0.152-0.185) were satisfactory, being within the appropriate range for powdered food quality. Total oil content, limonene retention values and antioxidant activity of the microparticles containing essential oil decreased in the presence of the carbohydrates. The addition of prebiotic biopolymers reduced the microparticle thermal stability. X-ray diffraction confirmed the amorphous characteristic of the microparticles and the interaction of the essential oil with the wall material. The presence of prebiotic biopolymers can be a good alternative for lime essential oil microparticles, mainly using fibre that has a functional food appeal and can improve consumer health.

Current Status of Magnetite-Based Core@Shell Structures for Diagnosis and Therapy in Oncology Short running title: Biomedical Applications of Magnetite@Shell Structures.

Superparamagnetic iron oxides, as magnetite (Fe3O4) or maghemite (γ-Fe2O3), are primary materials with intrinsic properties that enable them, as single components or as special composites, to base advanced techniques in medical clinical practices, as a contrast agent in magnetic resonance imaging (MRI), as magnetically-induced hyperthermic heat generator, and as a magnetic guide to locally deliver drugs to specific sites in the human body. An interesting approach to developing nanoplatforms for those applications consists in manufacturing core@shell nanostructures, in which the precursor magnetic iron oxide (usually, magnetite) acts as a core, and an organic, or inorganic compound is used as a shell in a multifunctional composite. In this review, we report the current advances in the use of magnetite-based core@shell nanostructures, including Fe3O4@SiO2 and Fe3O4@polymers, in MRI, magnetic hyperthermia and drug delivery systems for diagnosis and therapy of tumor cells. The development of nanoplatforms for combined therapy and diagnostic (theranostic) is also addressed.

Influence of recovering collagen with bioactive glass on osteoblast behavior.

Bioactive ceramics have interesting properties from the biological standpoint, but their effects on cellular events remain partially unknown. In the current work, we investigated cellular viability, proliferation, and metabolic activity of rat primary osteoblasts in contact with four different samples: type I collagen, bioactive glass-coated collagen (GC), and both samples submitted to immersion for 5 days in a simulated body fluid. The bioactive glass coating was obtained from a sol-gel process. The cell viability, the alkaline phosphate, the collagen secretion, and the nitric oxide production by osteoblast were measured after 72 h of incubation in the presence of the samples. The GC that was immersed for 5 days in a simulated body fluid solution showed an increase in osteoblast viability and proliferation when it was compared with control and the other samples.

In vivo performance of a sol-gel glass-coated collagen.

Synthetic bioactive materials offer possibilities to repair large tissue defects. It is well known that bioactivity, angiogenesis, and inflammation are key events in implant incorporation. Using glass-coated and glass-free collagen as potential bone graft substitutes, we carried out in vitro bioactivity and an in vivo angiogenesis and inflammation studies. The in vitro study showed bioactivity when the glass-coated samples were left in SBF for 5 days. This was confirmed by FTIR results, which presented P--O vibration bands characteristic of hydroxyapatite close to 1060 cm(-1) and 600 cm(-1). The in vivo response was evaluated following subcutaneous implantation of the biomaterial in the mouse dorsa. Angiogenesis, as determined by hemoglobin content extracted from implants 7 and 14 days after implantation, increased progressively in both glass-coated and glass-free collagen implants. However, vascularization was higher in the glass-coated collagen implants 14 days after implantation (mug Hb per mg wet tissue 6.0 +/- 0.3) compared with the glass-free group (1.6 +/- 0.1). The inflammatory process, determined by the levels of myeloperoxidase and N-acetylglucosaminidase, was similar for both implants. This study shows that glass-coated collagen implants hold osteogenic and angiogenic potential and may be used in clinical conditions requiring improvement of these biological processes.