Titanate nanoparticles for biodelivery of gold

Objectives: Titanate nanoparticles are ceramics that strongly bind specific metal ions or compounds. Our interdisciplinary group is investigating novel uses for these ceramics, including drug delivery for dental applications. We have shown previously that titanates bind gold and gold-based compounds, and are not cytotoxic to fibroblasts or monocytes when used alone. Our goal was to establish that nanoparticles loaded with Au compounds could deliver Au compounds to cells, thereby opening the possibility of using loaded nanoparticles to deliver metallo-based antimicrobials, anti-neoplastic agents, or anti-arthritics to treat oral-facial disease. Methods: We exposed monocytes (THP1) or fibroblasts (L929) to titanate nanoparticles (0.1-50 µg/mL) loaded with Au(III) ions or Auranofin® (AF), both known to inhibit cell mitochondrial activity. After exposures of 24-72 h, cell mitochondrial activity (n=8/ condition) was estimated using the MTT assay. Controls included titanates or Au compounds alone. Results: THP1 monocytes showed no mitochondrial suppression after exposure to any loaded titanate, yet both AF or Au(III) alone totally suppressed mitochondrial activity above 1 µM or 300 µM, respectively. Mitochondrial activity in L929 fibroblasts was suppressed by up to 90% or 40% (vs. titanates alone) after exposure to nanoparticles loaded with Au(III) or AF, respectively (p < 0.05). Mitochondrial suppression increased with time of exposure, suggesting ongoing delivery of the Au compounds to the fibroblasts. The fibroblasts also were more sensitive than monocytes to the Au compounds alone (p < 0.05), with >90% mitochondrial suppression above 0.4 µM (AF) or 50 µM (Au(III)). Conclusion: Our results show that titanate nanoparticles may be used to deliver Au compounds to cells, that different compounds exhibit different delivery behaviors, and that differential responses among cell types are possible. (Funded by SRNL and MCG Dental Research Centers)