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Development of multi-functional nanocarrier of siDNA and application for bone and joint diseases

siDNA多功能纳米载体的研制及其在骨关节疾病中的应用

基本信息

批准号：
17390412
负责人：
ITAKA Keiji
金额：
$ 10.55万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390412/
关键词：
siRNA delivery system nanocarrier bone and joint disease nanotechnology polyplex micelle

项目摘要

In this project, we developed the nanocarriers containing siRNA and analyzed the biological functions.1. Molucular design of nanocarriers The nanocarriers were composed of siRNA (or siRNA conjugate) and cationic polymers. The formation of nanocarriers with narrow distribution was confirmed.2. Growth inhibition of cultured cells on the spheroid culture system After applying RecQL1 siRNA using this nanocarrier, the growth of spheroid-shaped cells was effectively inhibited after a week of application. This effect was observed in a low concentration, indicating the stability of nanocarriers in the physiological condition, smooth penetration inside the spheroids, and facilitated uptake by the receptor-targeting ligands.3. Evaluation of biocompatibility By the evaluation of cytotoxicity and biocompatibility using cultured cells, this nanocarrier was revealed to have minimal cytotoxicity. In addition, the expressions of house-keeping genes were not affected by the nanocarrier, indicating the excellent biocompatibility.4. In vivo bone regeneration This nanocarrier was revealed to have good capacity for inducing cell differentiation, due to the high transfection efficiency, excellent biocompatibility and a sustained manner of gene expression. By applying this nanocarrier to the bone-defect model of mice, the better bone regeneration was induced compared to that by the adenoviral vector. We are planning to apply the siRNA nanocarriers to the in vivo studies with modifications such as installation of disulfide bonds into the carriers.

本课题主要研究了siRNA纳米载体的制备及其生物学功能.纳米载体的分子设计纳米载体由siRNA（或siRNA缀合物）和阳离子聚合物组成。证实了纳米载体的形成，且纳米载体分布较窄.在使用该纳米载体施加RecQL1 siRNA后，在施加一周后，球形细胞的生长被有效抑制。在低浓度下观察到这种效果，表明纳米载体在生理条件下稳定，在球状体内平滑渗透，并促进受体靶向配体的摄取.生物相容性评价通过使用培养的细胞评价细胞毒性和生物相容性，显示该纳米载体具有最小的细胞毒性。此外，纳米载体不影响管家基因的表达，具有良好的生物相容性.体内骨再生由于高转染效率、优异的生物相容性和持续的基因表达方式，这种纳米载体被揭示具有良好的诱导细胞分化的能力。通过将这种纳米载体应用于小鼠骨缺损模型，与腺病毒载体相比，诱导了更好的骨再生。我们计划将siRNA纳米载体应用于体内研究，并进行修改，例如在载体中安装二硫键。