A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy

被引:350
作者
Zhang, Ge [1 ]
Guo, Baosheng [1 ]
Wu, Heng [1 ]
Tang, Tao [1 ]
Zhang, Bao-Ting [1 ,2 ]
Zheng, Lizhen [1 ]
He, Yixin [1 ]
Yang, Zhijun [3 ]
Pan, Xiaohua [4 ]
Chow, Heelum [5 ]
To, Kinwah [5 ]
Li, Yaping [6 ]
Li, Dahu [7 ]
Wang, Xinluan [1 ]
Wang, Yixiang [8 ]
Lee, Kwongman [9 ]
Hou, Zhibo [10 ]
Dong, Nan [11 ]
Li, Gang [1 ]
Leung, Kwoksui [1 ]
Hung, Leungkim [1 ]
He, Fuchu [7 ]
Zhang, Lingqiang [7 ]
Qin, Ling [1 ,12 ]
机构
[1] Chinese Univ Hong Kong, Musculoskeletal Res Lab, Dept Orthopaed & Traumatol, Hong Kong, Hong Kong, Peoples R China
[2] Chinese Univ Hong Kong, Sch Chinese Med, Hong Kong, Hong Kong, Peoples R China
[3] Hong Kong Baptist Univ, Sch Chinese Med, Hong Kong, Hong Kong, Peoples R China
[4] Ji Nan Univ, Dept Orthoped, Hosp Med Coll 2, Shenzhen Peoples Hosp, Shenzhen, Peoples R China
[5] Chinese Univ Hong Kong, Sch Pharm, Hong Kong, Hong Kong, Peoples R China
[6] Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Delivery Syst, Shanghai 200031, Peoples R China
[7] Beijing Inst Radiat Med, State Key Lab Prote, Beijing Proteome Res Ctr, Beijing, Peoples R China
[8] Chinese Univ Hong Kong, Dept Imaging & Intervent Radiol, Hong Kong, Hong Kong, Peoples R China
[9] Chinese Univ Hong Kong, Lee Hysan Clin Res Lab, Hong Kong, Hong Kong, Peoples R China
[10] Jinan Univ, Biomed Res & Dev Ctr, Guangdong Prov Key Lab Bioengn Med, Natl Engn Res Ctr Genet Med, Guangzhou, Guangdong, Peoples R China
[11] Nankai Univ, Inst Mol Biol, Tianjin, Peoples R China
[12] Shenzhen Inst Adv Technol, Translat Med Res & Dev Ctr, Inst Biomed & Hlth Engn, Shenzhen, Peoples R China
关键词
PARATHYROID-HORMONE; POSTMENOPAUSAL WOMEN; COMBINATION; ALENDRONATE; DEPOSITION; FRACTURES; DOMAINS;
D O I
10.1038/nm.2617
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Metabolic skeletal disorders associated with impaired bone formation are a major clinical challenge. One approach to treat these defects is to silence bone-formation-inhibitory genes by small interference RNAs (siRNAs) in osteogenic-lineage cells that occupy the niche surrounding the bone-formation surfaces. We developed a targeting system involving dioleoyl trimethylammonium propane (DOTAP)-based cationic liposomes attached to six repetitive sequences of aspartate, serine, serine ((AspSerSer)(6)) for delivering siRNAs specifically to bone-formation surfaces. Using this system, we encapsulated an osteogenic siRNA that targets casein kinase-2 interacting protein-1 (encoded by Plekho1, also known as Plekho1). In vivo systemic delivery of Plekho1 siRNA in rats using our system resulted in the selective enrichment of the siRNAs in osteogenic cells and the subsequent depletion of Plekho1. A bioimaging analysis further showed that this approach markedly promoted bone formation, enhanced the bone micro-architecture and increased the bone mass in both healthy and osteoporotic rats. These results indicate (AspSerSer)(6)-liposome as a promising targeted delivery system for RNA interference- based bone anabolic therapy.
引用
收藏
页码:307 / 314
页数:8
相关论文
共 28 条
[1]  
Aubin J.E., 2002, PEDIAT BONE, P43
[2]   The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis [J].
Black, DM ;
Greenspan, SL ;
Ensrud, KE ;
Palermo, L ;
McGowan, JA ;
Lang, TF ;
Garnero, P ;
Bouxsein, ML ;
Bilezikian, JP ;
Rosen, CJ .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 349 (13) :1207-1215
[3]   Daily and cyclic parathyroid hormone in women receiving alendronate [J].
Cosman, F ;
Nieves, J ;
Zion, M ;
Woelfert, L ;
Luckey, M ;
Lindsay, R .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (06) :566-575
[4]  
CULLIS P R, 1989, Advanced Drug Delivery Reviews, V3, P267, DOI 10.1016/0169-409X(89)90024-0
[5]   Targeting Liposomes Toward Novel Pediatric Anticancer Therapeutics [J].
Federman, Noah ;
Denny, Christopher T. .
PEDIATRIC RESEARCH, 2010, 67 (05) :514-519
[6]   Differential cell surface expression of the STRO-1 and alkaline phosphatase antigens on discrete developmental stages in primary cultures of human bone cells [J].
Gronthos, S ;
Zannettino, ACW ;
Graves, SE ;
Ohta, S ;
Hay, SJ ;
Simmons, PJ .
JOURNAL OF BONE AND MINERAL RESEARCH, 1999, 14 (01) :47-56
[7]   Bone recognition mechanism of porcine osteocalcin from crystal structure [J].
Hoang, QQ ;
Sicheri, F ;
Howard, AJ ;
Yang, DSC .
NATURE, 2003, 425 (6961) :977-980
[8]   Parathyroid hormone and teriparatide for the treatment of osteoporosis: A review of the evidence and suggested guidelines for its use [J].
Hodsman, AB ;
Bauer, DC ;
Dempster, DW ;
Dian, L ;
Hanley, DA ;
Harris, ST ;
Kendler, DL ;
McClung, MR ;
Miller, PD ;
Olszynski, WP ;
Orwoll, E ;
Yuen, CK .
ENDOCRINE REVIEWS, 2005, 26 (05) :688-703
[9]   Involvement of FcRγ in signal transduction of osteoclast-associated receptor (OSCAR) [J].
Ishikawa, S ;
Arase, N ;
Suenaga, T ;
Saita, Y ;
Noda, M ;
Kuriyama, T ;
Arase, H ;
Saito, T .
INTERNATIONAL IMMUNOLOGY, 2004, 16 (07) :1019-1025
[10]   Bone regeneration by regulated in vivo gene transfer using Biocompatible polyplex nanomicelles [J].
Itaka, Keiji ;
Ohba, Shinsuke ;
Miyata, Kanjiro ;
Kawaguchi, Hiroshi ;
Nakamura, Kozo ;
Takato, Tsuyoshi ;
Chung, Ung-Il ;
Kataoka, Kazunori .
MOLECULAR THERAPY, 2007, 15 (09) :1655-1662