Osteoblast-Targeting-Peptide Modified Nanoparticle for siRNA/microRNA Delivery
- ACS Nano. 2016 Jun 28;10(6):5759-68. doi: 10.1021/acsnano.5b07828.
- 1. Department of Oral Implantology, School of Stomatology, Tongji University , Shanghai 200072, China.
- 2. Shanghai Engineering Research Center of Tooth Restoration and Regeneration , Shanghai 200072, China.
- 3. Sino-Russian Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University , Harbin 150086, China.
- 4. Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University , Guangzhou 510632, China.
- 5. The First Affiliated Hospital of Jinan University , Guangzhou 510632, China.
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.