表面修饰适配体S6的聚乳酸-羟基乙酸/聚乙二醇共聚物纳米粒制备及其运载小干扰RNA的应用研究

doi:10.6023/cjoc201803050

有机化学 ›› 2018, Vol. 38 ›› Issue (10): 2706-2712.DOI: 10.6023/cjoc201803050 上一篇下一篇

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表面修饰适配体S6的聚乳酸-羟基乙酸/聚乙二醇共聚物纳米粒制备及其运载小干扰RNA的应用研究

刘洋^a, 谢栓栓^a, 曾洁^a, 谈敏^a, 宋小莲^a, 朱君^b, 王昌惠^a

a 同济大学附属上海市第十人民医院上海 200072;
b 纳米技术及应用国家工程研究中心上海 200241

收稿日期:2018-03-29 修回日期:2018-06-19 发布日期:2018-06-22
通讯作者: 王昌惠,E-mail:wangch@tongji.edu.cn;朱君,E-mail:yzjzhu@163.com E-mail:wangch@tongji.edu.cn;yzjzhu@163.com
基金资助:
国家自然科学基金（No.81472180）资助项目.

Preparation of Poly (lactic-co-glycolic acid)/Polyethylene Glycol Nanoparticles with Surface-Modified Aptamer S6 and Its Application on Carrier siRNA

Liu Yang^a, Xie Shuanshuan^a, Zeng Jie^a, Tan Min^a, Song Xiaolian^a, Zhu Jun^b, Wang Changhui^a

a Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072;
b National Engineering Research Center for Nanotechnology, Shanghai 200241

Received:2018-03-29 Revised:2018-06-19 Published:2018-06-22
Contact: 10.6023/cjoc201803050 E-mail:wangch@tongji.edu.cn;yzjzhu@163.com
Supported by:
Project supported by the National Natural Science Foundation of China (No. 81472180).

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摘要/Abstract

肺癌是目前对人类健康威胁最大的恶性肿瘤之一，亟需新的诊治方法.本研究以核酸固相磷酰亚胺法合成适配体S6，再以偶联法制备了聚乳酸-羟基乙酸/聚乙二醇（PLGA-PEG）共聚物分子，进一步以1-（3-二甲氨基丙基）-3-乙基碳二亚胺盐酸盐（EDC）和N-羟基琥珀酰亚胺（NHS）为媒介，得到了一种具有生物靶向性的纳米载体材料PLGA-PEG-S6-CY3.以该载体材料包裹运载针对腺苷酸环化酶关联蛋白1（CAP1）的小干扰RNA（siRNA），构建了PLGA-PEG-S6-CY3/CAP1-siRNA纳米粒，可靶向性地运载CAP1-siRNA，从而抑制肺癌A549细胞的侵袭性.采用核磁共振氢谱表征了S6和PLGA-PEG分子结构，验证了其靶向性，检测了PLGA-PEG纳米粒与CAP1-siRNA的结合和释放，并进一步考察了该复合物抑制肿瘤细胞侵袭性的作用.结果表明，表面修饰适配体S6的PLGA-PEG纳米粒具有靶向性和运载siRNA的能力，可在体外下调肺癌A549细胞CAP1的表达，从而降低其侵袭性.

关键词: 适配体, PLGA-PEG分子, 小干扰RNA, 抗肿瘤侵袭

Lung cancer threats human health. The poly (lactic-co-glycolic acid)/polyethylene glycol (PLGA-PEG) was synthesized by the coupling method and aptamer S6 was synthesized by the nucleic acid solid-phase phosphorimide method. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide salt was obtained. Acid-mediated (EDC) and N-hydroxysuccinimide (NHS) mediators have resulted in a biotargeting nanocarrier material PLGA-PEG-S6-CY3. PLGA-PEG-S6-CY3/CAP1-siRNA nanoparticles were constructed by carrying the small interfering RNA (CAP1-siRNA) targeting the adenylate cyclase-associated protein 1 through the carrier material, and the sustained release of the CAP1-siRNA was achieved to achieve targeting inhibition of metastasis of non-small cell lung cancer A549 cells. The molecular structures of S6 and PLGA-PEG were characterized by nuclear magnetic resonance spectroscopy and their targeting properties were verified. The binding and release of PLGA-PEG nanoparticles and CAP1-siRNA were detected. Furthermore, the effect of the complex on inhibiting the invasiveness of tumor cells was further investigated. The results showed that the PLGA-PEG molecule prepared by the coupling method was used as the carrier, and the aptamer S6 was synthesized and used to modify PLGA-PEG. The obtained PLGA-PEG nanocomposite has the ability of targeting and carrying siRNA, and can be used in vitro. It can also down-regulate the expression of CAP1 in lung cancer A549 cells and reduce its invasiveness.

Key words: aptamer, PLGA-PEG molecule, siRNA, anti-tumor invasion References

引用此文

刘洋, 谢栓栓, 曾洁, 谈敏, 宋小莲, 朱君, 王昌惠. 表面修饰适配体S6的聚乳酸-羟基乙酸/聚乙二醇共聚物纳米粒制备及其运载小干扰RNA的应用研究[J]. 有机化学, 2018, 38(10): 2706-2712.

Liu Yang, Xie Shuanshuan, Zeng Jie, Tan Min, Song Xiaolian, Zhu Jun, Wang Changhui. Preparation of Poly (lactic-co-glycolic acid)/Polyethylene Glycol Nanoparticles with Surface-Modified Aptamer S6 and Its Application on Carrier siRNA[J]. Chin. J. Org. Chem., 2018, 38(10): 2706-2712.

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表面修饰适配体S6的聚乳酸-羟基乙酸/聚乙二醇共聚物纳米粒制备及其运载小干扰RNA的应用研究

Preparation of Poly (lactic-co-glycolic acid)/Polyethylene Glycol Nanoparticles with Surface-Modified Aptamer S6 and Its Application on Carrier siRNA

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