Cancer Inhibition and In Vivo Osteointegration and Compatibility of Gallium-Doped Bioactive Glasses for Osteosarcoma Applications

ACS Appl Mater Interfaces. 2022 Oct 12;14(40):45156-45166. doi: 10.1021/acsami.2c12102. Epub 2022 Sep 28.

Abstract

Traditional osteosarcoma therapies tend to focus solely on eradicating residual cancer cells and often fail to promote local bone regeneration and even inhibit it due to lack of precise control over target cells, i.e., the treatment affects both normal and cancer cells. Typically, multistep procedures are required for optimal efficacy. Here, we found that a silica-based bioactive material containing 3 mol % gallium oxide selectively kills human osteosarcoma cells and presents excellent in vivo osteointegration, while showing no local or systemic toxicity. Cell culture media conditioned with the proposed material was able to kill 41% of osteosarcoma cells, and no significant deleterious effect on normal human osteoblasts was observed. In addition, rats treated with the gallium-doped material showed excellent material-bone integration with no sign of local toxicity or implant rejection. Systemic biocompatibility investigation did not indicate any sign of toxicity, with no presence of fibrosis or cellular infiltrate in the histological microstructure of the liver and kidneys after 56 days of observation. Taken together, these results show that synergistic bone regeneration and targeted cancer therapy can be combined, paving the way toward new bone cancer treatment approaches.

Keywords: biocompatibility; bioglass; bone cancer; gallium; in vitro toxicity; in vivo regeneration.

MeSH terms

  • Animals
  • Bone Neoplasms* / drug therapy
  • Gallium* / chemistry
  • Gallium* / pharmacology
  • Glass / chemistry
  • Humans
  • Osteosarcoma* / drug therapy
  • Rats
  • Silicon Dioxide

Substances

  • Silicon Dioxide
  • Gallium