Engineered Biomimetic Nanovesicles Derived From Bone Marrow Stromal Cells With Innate Homing Capability for Targeted Delivery

Precise delivery of pharmaceuticals administered to bone marrow for various bone diseases is challenging, given the bone marrow-blood barrier (MBB). Bone marrow stromal cells (BMSCs) derived from bone marrow can naturally infiltrate the MBB and home to bone tissue. Here, biomimetic nanovesicles (namely mNVs) engineered with the extracted cell membrane from BMSCs are reported for homing delivery of different core nanomedicines to bone marrow. The cargo-loaded mNVs exhibited excellent bone targeting in crossing natural barriers is demonstrated to augment drug concentrations in bone marrow, and the bio-function of mNVs is verified in typical models of chronic metabolic bone disease and metastatic carcinoma. In the induced osteoporosis model, engineered mNVs deliver the nanocore of teriparatide-loaded poly(lactic-co-glycolic acid), forming a sustained-release system of teriparatide, which can significantly slow bone loss, maintain bone mass, and alleviate osteoporosis indicators. In osseous and systematic metastatic breast carcinoma models, the mNVs are employed to deliver DNA tetrahedron embedded doxorubicin and efficiently inhibit tumor progression and osteolytic lesions. This work suggests that high-efficiency bone marrow delivery of medications can be camouflaged by the cell membrane derived from BMSCs, initiating a new platform for bone targeting drug delivery for developing more effective therapeutics for bone diseases.