Designing macrophage membrane-engineered ruthenium/selenium nanoparticles to block bone metastasis of breast cancer

Bone metastasis along with osteolysis is a common complication of advanced breast cancer, which directly destroys bone function and becomes one of the major causes of cancer-related mortality. It is crucial to develop a new strategy to achieve effective cancer therapy and inhibition of osteolytic bone metastasis. Metal ruthenium (Ru) complexes exhibit therapeutic potential in cancer chemotherapy. However, the clinical applications of Ru complexes were limited by poor bioavailability, lacking targeting, nonspecific distribution. Therefore, in this study, engineering of cell membrane biomimetic modification was used to construct a highly biocompatible nanoplatform with carrying Ru metal complex of RuPOP and Se nanoparticles (SeNPs). Strikingly, the obtained RPSR nanoparticles can efficiently inhibit the proliferation, invasion and migration of breast cancer cells (MDA-MB-231 cells) in vitro. More importantly, RPSR nanoparticles can induce cycle arrest, apoptosis by generating excessive intracellular (reactive oxygen species, ROS) to disrupt the normal redox balance and induce DNA damage in tumor cells. Furthermore, RPSR nanoparticles can also reshape bone microenvironment by regulating selenoproteins to inhibit osteoclasts and avoid osteolytic bone metastasis induced by tumor development. Taken together, this study not only provides an effective cell membrane biomimetic strategy to enhance the shortcomings of metal complexes, but also demonstrates potential clinical significance for the combined treatment of anti-cancer and bone metastasis inhibition.