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介孔二氧化硅纳米颗粒细胞毒性和体内外分布研究

Research of the cytotoxicity and distribution of mesoporous silicate nanoparticles in vitro and in vivo

中文摘要英文摘要

通过RNA干扰技术沉默特定的基因(如NR2B)被认为是癌痛的一种新的治疗手段。但是,目前基因载体的安全性和低效率等问题严重制约了其临床应用。介孔二氧化硅纳米颗粒因为其较高生物相容性,生物可降解性和长时间的稳定性,可调、并且一致的孔径大小,易于修饰的表面特性,巨大表面积和比孔容等优点,在生物医学领域显现出巨大的潜在应用价值。本研究中制备出新型介孔二氧化硅纳米颗粒,以20nm四氧化三铁为核心包裹的二氧化硅颗粒,并且进行修饰使之表面氨基化,对此氨基改性的磁性介孔二氧化硅纳米颗粒细胞毒性研究,携带NR2B基因siRNA质粒细胞转染实验,以及此介孔二氧化硅纳米颗粒细胞培养以研究其在细胞的分布,和白鼠活体注射靶向模拟实验研究其在体内的生物分布。结果表明,在5ug/mL-125ug/mL浓度范围内,介孔二氧化硅纳米颗粒的细胞毒性不大,且在体内不会有蓄积作用,其最终会通过肾脏排出体外,生物安全性高。介孔二氧化硅纳米可以携带NR2B基因siRNA质粒通过胞吞作用进入细胞,在外加磁场诱导下可靶向到达病灶区域,为癌痛的靶向基因治疗奠定基础。

Researches show that gene therapy has broad application prospects in the treatment of cancer pain. NR2B gene interference will be a new therapy to treat cancer pain. But clinical practices have been critical restricted because of the safety problem and inefficiency of existing vectors. Among a variety of inorganic nanoparticles, mesoporous silicate nanoparticles (MSNs)have several attractive advantages for application as a new gene vector, such as good biocompatibiligy, biodegradability, good chemical and thermal stability, tunable pore size, dual-functional surfaces, large surface areas and pore volumes and so on, it likely to be a new choice of gene vector. Using sol-gel method, we use 20 nm Fe304 nanoparicles as a core , MSNs package Fe304 nanoparicles and then amino-modified the Fe304/Si02 nanocomposite materials . The structure and morphology of these particles were characterized by transmission electron microscopy. MTT and flowcytometry test show that the cytotoxicity of MSNs were low among the concentration 5ug/mL and 125ug/mL and NR2B gene siRNA plasmid can transfected by this functional modificated MSNs. We use the cell electron microscopy and the targeted stimulation experiment in vivo show that our MSNs can transport into cells, can metablised in vivo by kidney and can transported to targeted organ. Therefor we carry out the biological safety trials of MSN, and lay the foundation for the ultimately efficient, safe mesoporous silica vector used for gene therapy of cancer pain.

李沃、胡霞、黄东

医药卫生理论基础医学生物科学研究方法、生物科学研究技术

介孔二氧化硅纳米颗粒基因载体RNA干扰细胞毒性生物分布

mesoporous silica nanoparticlesgene carrierRNA interferencecytotoxicitybiodistribution

李沃,胡霞,黄东.介孔二氧化硅纳米颗粒细胞毒性和体内外分布研究[EB/OL].(2016-05-19)[2025-08-02].http://www.paper.edu.cn/releasepaper/content/201605-690.点此复制

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