A strategy for challenging tumorous bone regeneration by utilizing borosilicate bioactive glass synchronously boosting osteosarcoma combating and osteogenesis promotion of moderate magnetic hyperthermia
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE294487 | GEO | 2025/04/20
REPOSITORIES: GEO
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Project description:Sol-gel-derived bioactive glass nanoparticles have attracted special interest due to their potential as novel therapeutic and regenerative agents. Significant challenges are yet to be addressed. The fabrication of sol-gel-derived nanoparticles in binary and ternary systems with an actual composition that meets the nominal has to be achieved. This work addresses this challenge and delivers nanoparticles in a ternary system with tailored composition and particle size. It also studies how specific steps in the fabrication process can affect the incorporation of the metallic ions, nanoparticle size, and mesoporosity. Sol-gel-derived bioactive glass nanoparticles in the 62 SiO2-34.5 CaO-3.2 P2O5 (mol %) system have been fabricated and characterized for their structural, morphological, and elemental characteristics using Fourier transform infrared spectroscopy, X-ray diffraction analysis, scanning electron microscopy associated with elemental analysis, transmission electron microscopy, and solid-state nuclear magnetic resonance. The fabricated nanoparticles were additionally observed to form the apatite phase when immersed in simulated body fluid. This work highlights the effect of the different processing variables, such as the nature of the solvent, the order in which reagents are added, stirring time, and the concentrations in the catalytic solution on the controlled incorporation of specific ions (e.g., P and Ca) in the nanoparticle network and particle size.
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Project description:Hyperthermia - application of supra-physiological temperatures to cells, tissues or organs - is a pleiotropic treatment that affects most aspects of cellular metabolism, but its effects on DNA are of special interest in the context of cancer research and treatment. Hyperthermia inhibits repair of various DNA lesions, including double-strand breaks (DSBs), making it a powerful radio- and chemosensitizer, with proven clinical efficacy in therapy of various types of cancer, including tumors of head and neck, bladder, breast and cervix. Among the challenges for hyperthermia-based therapies are the transient character of its effects, the technical difficulties in maintaining uniformly elevated tumor temperature and the acquisition of thermotolerance. Approaches to reduce or eliminate these challenges could simplify the application of hyperthermia, boost its efficacy and improve treatment outcomes. Here we show that a single, short treatment with a relatively low dose of HSP90 inhibitor Ganetespib potentiates cytotoxic as well as radio- and chemosensitizing effects of hyperthermia and reduces thermotolerance in cervix cancer cell lines. Ganetespib alone, applied at this low dose, has virtually no effect on survival of non-heated cells. Our results thus suggest that HSP90 inhibition can be a safe, simple and efficient approach to improving hyperthermia treatment efficacy and reducing thermotolerance, paving the way for in vivo studies.
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Project description:In this work we synthesized mesoporous bioactive glass nanospheres (nMBG) with the aim to utilize them as substrates for loading one of the most potent amino-bisphosphonates, alendronate (AL). The results of the chemical and structural characterization show that the nMBG display a relatively high surface area (528 m²/g) and a mean pore volume of 0.63 cm³/g, both of which decrease on increasing alendronate content. It is possible to modulate the amount of AL loaded into the nanospheres up to a maximum value of about 17 wt %. In vitro tests were performed using a human osteosarcoma cell line (MG63) and a murine monocyte/macrophage cell line as osteoclast model (RAW 264.7). The results indicate that even the lower concentration of alendronate provokes decreased tumor cell viability, and that osteoclast activity exhibits an alendronate dose-dependent inhibition. The data suggest that nMBG can act as a suitable support for the local delivery of alendronate, and that the antiresorptive and antitumor properties of the functionalized mesoporous nanospheres can be modulated by varying the amount of alendronate loading.
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Project description:Mesoporous bioactive glasses (MBGs) are promising materials for regenerative medicine, due to their favorable properties including bioactivity and degradability. These key properties, but also their surface area, pore structure and pore volume are strongly dependent on synthesis parameters and glass stoichiometry. However, to date no systematic study on MBG properties covering a broad range of possible compositions exists. Here, 24 MBG compositions in the SiO2-CaO-P2O5 system were synthesized by varying SiO2 (60-90 mol %), CaO and P2O5 content (both 0 to 40 mol-%), while other synthesis parameters were kept constant. Mesopore characteristics, degradability and bioactivity were analysed. The results showed that, within the tested range of compositions, mesopore formation required a molar SiO2 content above 60% but was independent of CaO and P2O5 content. While mesopore size did not depend on glass stoichiometry, mesopore arrangement was influenced by the SiO2 content. Specific surface area and pore volume were slightly altered by the SiO2 content. All materials were degradable; however, degradation as well as bioactivity, i.e. the ability to form a CaP mineral on the surface, depended on stoichiometry. Major differences were found in early surface reactions in simulated body fluid: where some MBGs induced direct hydroxyapatite crystallization, high release of calcium in others resulted in calcite formation. In summary, degradation and bioactivity, both key parameters of MBGs, can be controlled by glass stoichiometry over a broad range while leaving the unique structural parameters of MBGs relatively unaffected. This allows targeted selection of material compositions for specific regenerative medicine applications.
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