A delivery system specifically approaching bone resorption surfaces to facilitate therapeutic modulation of microRNAs in osteoclasts
Publication in refereed journal



摘要Dysregulated microRNAs in osteoclasts could cause many skeletal diseases. The therapeutic manipulation of these pathogenic microRNAs necessitates novel, efficient delivery systems to facilitate microRNAs modulators targeting osteoclasts with minimal off-target effects. Bone resorption surfaces characterized by highly crystallized hydroxyapatite are dominantly occupied by osteoclasts. Considering that the eight repeating sequences of aspartate (D-Asp(8)) could preferably bind to highly crystallized hydroxyapatite, we developed a targeting system by conjugating D-Asps peptide with liposome for delivering microRNA modulators specifically to bone resorption surfaces and subsequently encapsulated antagomir-148a (a microRNA modulator suppressing the osteoclastogenic miR-148a), i.e. (D-Asp(8))-liposome-antagomir-148a. Our results demonstrated that D-Asp(8) could facilitate the enrichment of antagomir-148a and the subsequent down-regulation of miR-148a in osteoclasts in vivo, resulting in reduced bone resorption and attenuated deterioration of trabecular architecture in osteoporotic mice. Mechanistically, the osteoclast-targeted delivery depended on the interaction between bone resorption surfaces and D-Asp(8). No detectable liver and kidney toxicity was found in mice after single/multiple dose(s) treatment of (D-Asp(8))-liposome-antagomir-148a. These results indicated that (D-Asp(8))-liposome as a promising osteoclast-targeting delivery system could facilitate clinical translation of microRNA modulators in treating those osteoclast-dysfunction-induced skeletal diseases. (C) 2015 Elsevier Ltd. All rights reserved.
著者Liu J, Dang L, Li DF, Liang C, He XJ, Wu H, Qian AR, Yang ZJ, Au DWT, Chiang MWL, Zhang BT, Han QB, Yue KKM, Zhang HQ, Lv CW, Pan XH, Xu JK, Bian ZX, Shang P, Tan WH, Liang ZC, Guo BS, Lu AP, Zhang G
頁次148 - 160
關鍵詞Bone resorption; MicroRNA; Osteoclast; Targeted delivery system
Web of Science 學科類別Engineering; Engineering, Biomedical; Materials Science; Materials Science, Biomaterials

上次更新時間 2020-21-09 於 00:57