title: Stimulation of apoptotic pathways in liver cancer cells: An alternative perspective on the biocompatibility and the utility of biomedical glasses.
abstract: A host of research opportunities with innumerable clinical applications are open to biomedical glasses if one considers their potential as therapeutic inorganic ion delivery systems. Generally, applications have been limited to repair and regeneration of hard tissues while compositions are largely constrained to the original bioactive glass developed in the 1960s. However, in oncology applications the therapeutic paradigm shifts from repair to targeted destruction. With this in mind, the composition-structure-property-function relationships of vanadium-containing zinc-silicate glasses (0.51SiO2-0.29Na2O-(0.20-X)ZnO-XV2O5, 0 ≤ X ≤ 0.09) were characterized in order to determine their potential as therapeutic inorganic ion delivery systems. Increased V2O5mole fraction resulted in a linear decrease in density and glass transition temperature (Tg).(29)Si MAS NMR peak maxima shifted upfield while(51)V MAS NMR peak maxima were independent of V2O5content and overlapped well with the spectra NaVO3 Increased V2O5mole fraction caused ion release to increase. When human liver cancer cells, HepG2, were exposed to these ions they demonstrated a concentration-dependent cytotoxic response, mediated by apoptosis. This work demonstrates that the zinc-silicate system studied herein is capable of delivering therapeutic inorganic ions at concentrations that induce apoptotic cell death and provide a simple means to control therapeutic inorganic ion delivery.
authors.affiliation: School of Biomedical Engineering, Dalhousie University, Halifax, Canada.
authors.forename: Nancy
authors.initials: N
authors.lastname: Kilcup
authors.affiliation: Regenerative Medicine Institute, Bioscience Research Building, National University of Ireland Galway, Galway, Ireland.
authors.forename: Seán
authors.initials: S
authors.lastname: Gaynard
authors.affiliation: Department of Chemistry and Institute for Research in Materials, Dalhousie University, Halifax, Canada.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Werner-Zwanziger
authors.affiliation: Department of Diagnostic Imaging and Interventional Radiology, QEII Health Sciences Centre, Victoria General Hospital, Victoria Building, Halifax, Canada Department of Diagnostic Radiology, Dalhousie University, Halifax, Canada.
authors.forename: Elena
authors.initials: E
authors.lastname: Tonkopi
authors.affiliation: Regenerative Medicine Institute, Bioscience Research Building, National University of Ireland Galway, Galway, Ireland.
authors.forename: Jessica
authors.initials: J
authors.lastname: Hayes
authors.affiliation: School of Biomedical Engineering, Dalhousie University, Halifax, Canada Department of Diagnostic Imaging and Interventional Radiology, QEII Health Sciences Centre, Victoria General Hospital, Victoria Building, Halifax, Canada Department of Applied Oral Sciences, Dentistry Building, Dalhousie University, Halifax, Canada d.boyd@dal.ca.
authors.forename: Daniel
authors.initials: D
authors.lastname: Boyd
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001672:Biocompatible Materials / Q000737:chemistry*; D016503:Drug Delivery Systems; D005898:Glass / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D007477:Ions / Q000008:administration & dosage* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008422:Materials Testing; D017640:Silicates / Q000737:chemistry*; D017968:Vanadium Compounds / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D007477:Ions; D017640:Silicates; D017968:Vanadium Compounds; D015032:Zinc
keywords: Targeted drug delivery; apoptosis; biocompatibility of biomedical glass; oncology; therapeutic inorganic ions