Osteoblast-Targeting-Peptide Modified Nanoparticle for siRNA/microRNA Delivery

Antiosteoporosis gene-based drug development strategies are presently focused on targeting osteoblasts to either suppress bone loss or increase bone mass. Although siRNA/microRNA-based gene therapy has enormous potential, it is severely limited by the lack of specific cell-targeting delivery systems. We report an osteoblast-targeting peptide (SDSSD) that selectively binds to osteoblasts <i>via</i> periostin. We developed SDSSD-modified polyurethane (PU) nanomicelles encapsulating siRNA/microRNA that delivers drugs to osteoblasts; the data showed that SDSSD–PU could selectively target not only bone-formation surfaces but also osteoblasts without overt toxicity or eliciting an immune response <i>in vivo</i>. We used the SDSSD–PU delivery system to deliver anti-miR-214 to osteoblasts and our results showed increased bone formation, improved bone microarchitecture, and increased bone mass in an ovariectomized osteoporosis mouse model. SDSSD–PU may be a useful osteoblast-targeting small nucleic acid delivery system that could be used as an anabolic strategy to treat osteoblast-induced bone diseases