Biomineralized mitochondrial transplantation corrects macrophage behaviour to suppress osteoporosis under breast cancer susceptibility

Abstract

Osteoporosis caused by bone metastasis in breast cancer patients is often exacerbated by existing therapies, primarily leading to bone loss. Macrophages play a vital role in breast cancer-induced bone loss, where their highly metabolic plasticity contributes to the bone loss process. Exogenous mitochondria offer a new approach for studying the intervention in intracellular metabolism. However, isolated mitochondria are highly vulnerable in vitro, which makes mitochondrial transplantation technology challenging. Therefore, we used zeolitic imidazolate framework-8 (ZIF-8), a type of metal-organic framework, to biomineralize mitochondria to improve the current difficulties. Due to its biocompatibility and protective structure, our results showed that ZIF-8 biomineralization prolonged isolated mitochondria preservation and enhanced exogenous mitochondrial transplantation efficiency. By undergoing mitochondrial behaviour correction in macrophages, we demonstrated that mitochondrial transplantation suppressed osteoporosis in breast cancer by inhibiting macrophages from differentiating into osteoclasts. In conclusion, this study provides a new possibility for the current problem in mitochondrial transplantation and offers new therapeutic potential in breast cancer-induced osteoporosis.