Stimulation of apoptotic pathways in liver cancer cells: An alternative perspective on the biocompatibility and the utility of biomedical glasses

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 V₂O₅ mole fraction resulted in a linear decrease in density and glass transition temperature (T_g). ²⁹Si MAS NMR peak maxima shifted upfield while ⁵¹V MAS NMR peak maxima were independent of V₂O₅ content and overlapped well with the spectra NaVO₃. Increased V₂O₅ mole 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.