Bone-targeted engineered bacterial extracellular vesicles delivering miRNA to treat osteoporosis

Osteoporosis (OP), characterized by decreased bone density and destruction of bone microstructure, is a common systemic bone disease in the elderly. Conventional therapies suffer from poor targeting and long-term toxicity. Engineered bacterial extracellular vesicles (BEVs) containing bioactive molecules show great potential as alternative OP therapies. Here, we developed a delivery system based on BEVs secreted probiotic Lactobacillus rhamnosus GG (LGG). Bone-targeting peptides were anchored on the LGG-EVs membranes, which endowed LGG-EVs the ability to deliver intrinsic miRNA to bone microenvironment. Bone-targeted LGG-EVs (BT-LGG-EVs) exhibited great bone targeting capability without significant toxicity. BT-LGG-EVs not only promoted osteogenic differentiation and mineralization but also inhibited the formation of osteoclasts. Furthermore, BT-LGG-EVs were demonstrated to be able to attenuate the OVX-induced osteoporotic phenotypes. Our study demonstrated that BT-LGG-EVs hold great promise for use as an innovative, safe, and effective solution for the treatment of OP.