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.

Anti-Trypanosoma cruzi Potential of Vestitol Isolated from Lyophilized Red Propolis.

Chagas disease (CD) is a worldwide public health problem, and the drugs available for its treatment have severe limitations. Red propolis is a natural extract known for its high content of phenolic compounds and for having activity against T. cruzi. The aim of this study was to investigate the trypanocidal potential of red propolis to isolate, identify, and indicate the mode of action of the bioactive compounds. The results revealed that the total phenolic content was 15.4 mg GAE/g, and flavonoids were 7.2 mg QE/g. The extract was fractionated through liquid-liquid partitioning, and the trypanocidal potential of the samples was evaluated using the epimastigote forms of the Y strain of T. cruzi. In this process, one compound was characterized by MS, 1H, and 13C NMR and identified as vestitol. Cytotoxicity was evaluated employing MRC-5 fibroblasts and H9C2 cardiomyocytes, showing cytotoxic concentrations above 15.62 µg/mL and 31.25 µg/mL, respectively. In silico analyses were applied, and the data suggested that the substance had a membrane-permeation-enhancing effect, which was confirmed through an in vitro assay. Finally, a molecular docking analysis revealed a higher affinity of vestitol with farnesyl diphosphate synthase (FPPS). The identified isoflavan appears to be a promising lead compound for further development to treat Chagas disease.

Anti-Inflammatory, Antimicrobial, Antioxidant and Photoprotective Investigation of Red Propolis Extract as Sunscreen Formulation in Polawax Cream.

Many activities have been described for propolis, including, antiviral, antibacterial, antifungal, anti-inflammatory, immunoregulatory, antioxidant and wound healing properties. Recently, propolis has been highlighted due to its potential application in the pharmaceutical and cosmetic industries, motivating a better understanding of its antioxidant and anti-inflammatory activities. Propolis and its main polyphenolic compounds presented high antioxidant activity, and effectiveness as broad spectrum UVB and UVA photoprotection sunscreens. Through a qualitative phytochemical screening, the ethanolic red propolis extracts (EEPV) (70% at room temperature and 70% at a hot temperature) presented a positive result for flavonoids and terpenoids. It presented an antioxidant activity for reducing 50% of DPPH of 17 and 12 µg/mL for extraction at room temperature and at a hot temperature, respectively. The UPLC-QTOF-MS/MS analysis allowed the annotation of 40 substances for EEPV-Heated and 42 substances for EEPV-Room Temperature. The IC50 results of the ABTS scavenging activity was 4.7 µg/mL for both extractions, at room temperature and at a hot temperature. Additionally, we also evaluated the cytotoxic profile of propolis extracts against macrophage (RAW 264.7 cells) and keratinocytes (HaCaT cells), which showed non-cytotoxic doses in cell viability assays even after a long period of exposure. In addition, propolis extracts showed antibacterial activity for Gram-positive bacteria (Staphylococcus aureus and Staphylococcus epidermidis), demonstrating potential biological activity for the creation of formulations aimed at disease control and prevention.

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.

Nanohybrid composed of graphene oxide functionalized with sodium hyaluronate accelerates bone healing in the tibia of rats.

This study synthesized and characterized a nanohybrid composed of graphene oxide (GO) functionalized with sodium hyaluronate (HY) (GO-HY), evaluated its effect in vitro and determined its osteogenic potential in vivo. The synthesized nanohybrid was analyzed by Scanning electron microscopy (SEM), Raman spectrometry, Thermogravimetry, Fourier-transform infrared (FTIR) spectroscopy and X-ray diffraction. MC3T3-E1 cell viability was assessed by MTT assay in 48 and 72 h. Bone defects were created in tibia of 40 Wistar rats and filled with blood clot (control), 1% HY, GO (50, 100 and 200 µg/mL) and the nanohybrid (50, 100 and 200 µg/mL). After 7 and 14 days, histomorphometric analysis was carried out to assess osteogenic potential of the nanohybrid. Immunohistochemical analysis evaluated the expression of vascular endothelial growth factor (VEGF) in bone defects. Thermogravimetric analysis, Raman and FTIR spectrometry confirmed the functionalization of GO with HY by covalent bonds. Five µg/mL concentrations of the nanohybrid did not alter the viability of the MC3T3-E1 cells. Histomorphometric analysis demonstrated that the nanohybrid at 100 µg/mL significantly accelerated the bone repair in tibia of rats when compared to controls (p < 0.01). Immunohistochemical analysis showed a significantly less intense VEGF expression in tibia treated with the nanohybrid when compared to controls (p < 0.05). The nanohybrid composed of GO functionalized with HY was able to induce the acceleration of the tissue regeneration process in bone defects created in the tibia of rats. This novel nanohybrid is a promising material for the field of bone tissue engineering.

Cobalt-containing bioactive glass mimics vascular endothelial growth factor A and hypoxia inducible factor 1 function.

Bioactive glasses (BGs) have shown great potential for tissue regeneration and their composition flexibility allows the incorporation of different ions with physiological activities and therapeutic properties in the glass network. Among the many ions that could be incorporated, cobalt (Co) is a significant one, as it mimics hypoxia, triggering the formation of new blood vessels by the vascular endothelial growth factor A (VEGFA), due to the stabilizing effect on the hypoxia inducible factor 1 subunit alpha (HIF1A), an activator of angiogenesis-related genes, and is therefore of great interest for tissue engineering applications. However, despite its promising properties, the effects of glasses incorporated with Co on angiogenesis, through human umbilical cord vein endothelial cells (HUVECs) studies, need to be further investigated. Therefore, this work aimed to evaluate the biocompatibility and angiogenic potential of a new sol-gel BG, derived from the SiO2 -CaO-P2 O5 -CoO system. The structural evaluation showed the predominance of an amorphous glass structure, and the homogeneous presence of cobalt in the samples was confirmed. in vitro experiments showed that Co-containing glasses did not affect the viability of HUVECs, stimulated the formation of tubes and the gene expression of HIF1A and VEGFA. in vivo experiments showed that Co-containing glasses stimulated VEGFA and HIF1A expression in blood vessels and cell nuclei, respectively, in the deep dermis layer of the dorsal region of rats, featuring considerable local stimulation of the angiogenesis process due to Co-release. Co-containing glasses showed therapeutic effect, and Co incorporation is a promising strategy for obtaining materials with superior angiogenesis properties for tissue engineering applications.

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.