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 via 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 in vivo. 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.