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
收稿日期: 2018-03-29
修回日期: 2018-06-19
网络出版日期: 2018-06-22
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
Received date: 2018-03-29
Revised date: 2018-06-19
Online published: 2018-06-22
Supported by
Project supported by the National Natural Science Foundation of China (No. 81472180).
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
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 . DOI: 10.6023/cjoc201803050
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
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