Development of dual acting selenium-doped hydroxyapatite nanoparticles with platinum-bisphosphonate complexes for bone cancer therapy

Abstract

Bone represents one of the most common sites for metastasis originating from solid tumors, especially breast and prostate cancers, causing severe complications like pain, fractures, and impaired quality of life. Hydroxyapatite (HA) nanoparticles (NPs) have been considered as good candidates for bone-targeted drug delivery due to their biocompatibility and osteoconductivity. In this study, we developed selenium-doped hydroxyapatite (HASe) NPs with reduced selenium content (up to 2.40 wt%) with the aim of overcoming the toxicity issues associated with previously reported higher Se doping levels. The HA-based NPs were thoroughly characterized to evaluate their morphological, colloidal, and compositional features, supporting the effective incorporation of selenium (Se) within the HA structure. In vitro cytotoxicity assays on MCF7wt breast cancer cells demonstrated a clear Se dose-dependent reduction in viability. To improve the anticancer potential, HA and selected HASe NPs were further functionalized with two HA-binding anti-tumor platinum-bisphosphonate (PtBP) complexes. The resulting PtBP-HASe NPs exhibited stronger cytotoxicity than PtBP-HA, despite their lower platinum content, highlighting an additional effect due to the presence of Se. Notably, PtBP-HASe NPs maintained a cytotoxic profile comparable to more highly doped HASe formulations, while reducing their Se content, potentially improving safety. Mechanistic investigations confirmed that reactive oxygen species (ROS) contribute to the antiproliferative activity of both the platinum complexes and the functionalized NPs, providing insight into the redox-mediated cytotoxicity of these nanomaterials. These findings suggest that PtBP-HASe NPs represent a promising dual-action biomaterial for bone-targeted cancer therapy, combining anticancer efficacy with enhanced biocompatibility potential.