包被交联PEI的拓孔介孔硅的制备与表征

doi:10.5246/jcps.2015.11.091

中国药学(英文版) ›› 2015, Vol. 24 ›› Issue (11): 712-720.DOI: 10.5246/jcps.2015.11.091

包被交联PEI的拓孔介孔硅的制备与表征

孙璐^1,2, 刘瑜洁^1,2, 仰浈臻^1,2, 齐宪荣^1,2,3*

1. 北京大学医学部分子药剂学与新释药系统北京市重点实验室, 北京 100191
2. 北京大学医学部药学院药剂学系, 北京 100191
3. 北京大学医学部天然药物及仿生药物国家重点实验室, 北京 100191

收稿日期:2015-05-17 修回日期:2015-06-20 出版日期:2015-11-20 发布日期:2015-07-20
通讯作者: Tel.: 86-10-82801584, E-mail: qixr@bjmu.edu.cn
基金资助:
National Natural Science Foundation of China (Grant No. 81273454 and 81473156), Beijing Nature Science Foundation (Grant No. 7132113), Doctoral Foundation of the Ministry of Education (Grant No. 20130001110055), National Key Basic Research Program (Grant No. 2013CB932501).

Preparation and characterization of mesoporous silica nanoparticles with enlarged pores capped with crosslinked PEI

Lu Sun^1,2, Yujie Liu^1,2, Zhenzhen Yang^1,2, Xianrong Qi^1,2,3*

1. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, Peking University Health Science Center, Beijing 100191, China
2. Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
3. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Sciences Center, Beijing 100191, China

Received:2015-05-17 Revised:2015-06-20 Online:2015-11-20 Published:2015-07-20
Contact: Tel.: 86-10-82801584, E-mail: qixr@bjmu.edu.cn
Supported by:
National Natural Science Foundation of China (Grant No. 81273454 and 81473156), Beijing Nature Science Foundation (Grant No. 7132113), Doctoral Foundation of the Ministry of Education (Grant No. 20130001110055), National Key Basic Research Program (Grant No. 2013CB932501).

摘要/Abstract

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siRNA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siRNA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。siRNA的载药量可达35 μg siRNA/mg MSNs。随后, MSN-siRNA/CrPEI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siRNA提高了420倍。MSN-siRNA/CrPEI可以成为siRNA的有效的递送策略, 可进一步进行抗肿瘤药效学的研究。

关键词: 介孔二氧化硅纳米粒, 制备, 聚乙烯亚胺, MCF-7细胞

Abstract:

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 siRNA 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 siRNA 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 siRNA (35 μg siRNA/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 siRNA loaded in the as-synthesized MSNs was readily internalized into MCF-7 cells and displayed 420 times higher intake than that of naked siRNA. The MSNs may be exploited to become an effective siRNA cell delivery strategy and further studied for the anti-tumor efficacy.

Key words: Mesoporous silica nanoparticle, Preparation, Polyethylenimine, MCF-7 cells

中图分类号:

R943

Supporting:

孙璐, 刘瑜洁, 仰浈臻, 齐宪荣. 包被交联PEI的拓孔介孔硅的制备与表征[J]. 中国药学(英文版), 2015, 24(11): 712-720.

Lu Sun, Yujie Liu, Zhenzhen Yang, Xianrong Qi. Preparation and characterization of mesoporous silica nanoparticles with enlarged pores capped with crosslinked PEI[J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(11): 712-720.

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包被交联PEI的拓孔介孔硅的制备与表征

Preparation and characterization of mesoporous silica nanoparticles with enlarged pores capped with crosslinked PEI

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