文献类型：期刊文献

英文题名：Rational polyelectrolyte nanoparticles endow preosteoclast-targeted siRNA transfection for anabolic therapy of osteoporosis

作者：Zhang, Zheng[1];Ding, Peng[2];Meng, Yichen[1];Lin, Tao[1];Zhang, Zhanrong[1];Shu, Haoming[1];Ma, Jun[3];Stuart, Martien Cohen[2];Gao, Yang[4];Wang, Junyou[2];Zhou, Xuhui[1,5]

机构：[1]Naval Med Univ, Mil Med Univ 2, Changzheng Hosp, Dept Orthoped, Shanghai 200003, Peoples R China;[2]East China Univ Sci & Technol, State Key Lab Chem Engn, Shanghai 200237, Peoples R China;[3]Shanghai Jiao Tong Univ Sch Med, Shanghai Gen Hosp, Shanghai Peoples Hosp 1, Dept Orthoped, Shanghai 200080, Peoples R China;[4]Chinese Peoples Liberat Army Gen Hosp, Med Ctr 4, Dept Orthoped, Beijing 100048, Peoples R China;[5]Shanghai Jiao Tong Univ Sch Med, Shanghai Gen Hosp, Shanghai Peoples Hosp 1, Translat Res Ctr orthoped, Shanghai 200080, Peoples R China

年份：2023

卷号：9

期号：10

外文期刊名：SCIENCE ADVANCES

收录：;EI(收录号：20231213744718);WOS:【SCI-EXPANDED(收录号:WOS:000960951400020)】；

基金：Acknowledgments Funding: This research was funded by the National Logistics Major Research Project (AWS18C001) , National Natural Science Foundation of China (82172516, 82002369) , Shanghai Sailing program (19YF1447800) , and 1000 Foreign Experts Program (WQ20163100341) . Author contributions: Zheng Zhang, P.D., J.W., and X.Z. conceived this project. P.D. synthesized the NPs. Zheng Zhang and Y.M. performed most of the in vitro and in vivo experiments. T.L., Zhanrong Zhang, H.S., J.M., and Y.G. contributed to the performance of the NP administration, histological analysis, and flow cytometry in animal studies. Y.G., J.W., and X.Z. supervised the project. Zheng Zhang, P.D., and J.W. wrote the draft manuscript. Zheng Zhang, P.D., M.C.S., Y.G., J.W., and X.Z. reviewed, edited, and formed the final manuscript. All authors contributed to the revisions of the manuscript. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.

语种：英文

外文关键词：Bone - Core shell nanoparticles - Diseases - Mammals

摘要：Targeted transfection of siRNA to preosteoclasts features the potential of anti-osteoporosis, yet challenge arises from the development of satisfied delivery vehicles. Here, we design a rational core-shell nanoparticle (NP) com-posed of cationic and responsive core for controlled load and release of small interfering RNA (siRNA) and com-patible polyethylene glycol shell modified with alendronate for enhanced circulation and bone-targeted delivery of siRNA. The designed NPs perform well on transfection of an active siRNA (siDcstamp) that interferes Dcstamp mRNA expression, leading to impeded preosteoclast fusion and bone resorption, as well as promoted osteogenesis. In vivo results corroborate the abundant siDcstamp accumulation on bone surfaces and the en-hanced trabecular bone mass volume and microstructure in treating osteoporotic OVX mice by rebalancing bone resorption, formation, and vascularization. Our study validates the hypothesis that satisfied transfection of siRNA enables preserved preosteoclasts that regulate bone resorption and formation simultaneously as po-tential anabolic treatment for osteoporosis.