摘要
流行病学统计数据揭示了女性群体患癌频率高发的现状,以及对于新的治疗策略的迫切需要。本研究合成了一种代表性的无机纳米材料的纳米粒——介孔二氧化硅纳米粒递送小干扰RNA,并通过si RNA发挥基因沉默作用治疗乳腺癌。本研究对介孔二氧化硅纳米粒的合成的关键工序进行优化,使得所制备的纳米粒具有所需的性质,即通过拓孔来高载药量。装载si RNA进入介孔内后,用交联聚乙烯亚胺包被在介孔硅的表面,作为的孔的―保护帽‖,保护孔内的药物不被泄露。si RNA的载药量可达35μg si RNA/mg MSNs。随后,MSN-si RNA/Cr PEI作为药物递送系统在MCF-7细胞上进行体外水平的评价,结果表明该载体具有微弱的毒性和易于摄取的特性,摄取量比裸si RNA提高了420倍。MSN-si RNA/Cr PEI可以成为si RNA的有效的递送策略,可进一步进行抗肿瘤药效学的研究。
The epidemiological statistics reveals the striking patterns of cancer in women and highlights the need for novel therapeutic strategies. In this work, mesoporous silica nanoparticles(MSNs) as representative of inorganic nanoparticles were prepared for loading si RNA that plays a role of gene silencing to treat breast carcinoma(MCF-7) cells. The critical processes of synthesis were optimized for the nanoparticles with desired quality attributes that have the enlarged pores for elevated loading capacity. After si RNA loading into mesoporous, crosslinked-polyethylenimine was employed as the cap to coat the enlarged MSN pores and protect the cargo from leakage. The elevated quantity of si RNA(35 μg si RNA/mg MSNs) were loaded in the MSNs. The as-synthesized MSNs were further evaluated on MCF-7 cells in vitro and shown negligible cytotoxicity. As expected, the si RNA loaded in the as-synthesized MSNs was readily internalized into MCF-7 cells and displayed 420 times higher intake than that of naked si RNA. The MSNs may be exploited to become an effective si RNA cell delivery strategy and further studied for the anti-tumor efficacy.
基金
National Natural Science Foundation of China(Grant No.81273454 and 81473156)
Beijing Nature Science Fo undation(Grant No.7132113)
Doctoral Foundation of the Ministry of Education(Grant No.20130001110055)
National Key Ba sic Research Program(Grant No.2013CB932501)