title: Osteoblast-Targeting-Peptide Modified Nanoparticle for siRNA/microRNA Delivery.
abstract: 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.
authors.affiliation: Department of Oral Implantology, School of Stomatology, Tongji University , Shanghai 200072, China.|Shanghai Engineering Research Center of Tooth Restoration and Regeneration , Shanghai 200072, China.|Sino-Russian Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University , Harbin 150086, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University , Guangzhou 510632, China.
authors.forename: Xiongzhen
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Oral Implantology, School of Stomatology, Tongji University , Shanghai 200072, China.
authors.forename: Mingxiang
authors.initials: M
authors.lastname: Cai
authors.affiliation: The First Affiliated Hospital of Jinan University , Guangzhou 510632, China.
authors.forename: Xiangning
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University , Guangzhou 510632, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Oral Implantology, School of Stomatology, Tongji University , Shanghai 200072, China.
authors.forename: Chenyang
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University , Guangzhou 510632, China.
authors.forename: Yayu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University , Guangzhou 510632, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University , Guangzhou 510632, China.
authors.forename: Jiafan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University , Guangzhou 510632, China.
authors.forename: Shannai
authors.initials: S
authors.lastname: Li
authors.affiliation: Sino-Russian Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University , Harbin 150086, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Kang
authors.affiliation: Sino-Russian Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University , Harbin 150086, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Oral Implantology, School of Stomatology, Tongji University , Shanghai 200072, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Oral Implantology, School of Stomatology, Tongji University , Shanghai 200072, China.|Shanghai Engineering Research Center of Tooth Restoration and Regeneration , Shanghai 200072, China.
authors.forename: Zuolin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University , Guangzhou 510632, China.
authors.forename: An
authors.initials: A
authors.lastname: Hong
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University , Guangzhou 510632, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D051379:Mice; D035683:MicroRNAs; D053758:Nanoparticles; D010006:Osteoblasts; D010012:Osteogenesis; D010455:Peptides; D034741:RNA, Small Interfering
chemical_list: D035683:MicroRNAs; D010455:Peptides; D034741:RNA, Small Interfering
keywords: bone formation; gene delivery; osteoblast targeting peptide; osteoporosis therapy; polyurethane nanoparticle