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

作　　者：刘洋[1] 谢栓栓[1] 曾洁 谈敏[1] 宋小莲[1] 朱君[2] 王昌惠[1] Liu Yang;Xie Shuanshuan;Zeng Jie;Tan Min;Song Xiaolian;Zhu Jun;Wang Changhui(Department of Respiratory Medicine,Shanghai Tenth People＇s Hospital,Tongji University,Shanghai 200072;National Engineering Research Center for Nanotechnology,Shanghai 200241)

机构地区：[1]同济大学附属上海市第十人民医院,上海200072 [2]纳米技术及应用国家工程研究中心,上海200241

出　　处：《有机化学》2018年第10期2706-2712,共7页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.81472180)资助项目~~

摘　　要：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(si RNA),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-si RNA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si RNA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.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.

关 键 词：适配体 PLGA-PEG分子 小干扰RNA 抗肿瘤侵袭 

分 类 号：R943[医药卫生—药剂学] TB383.1[医药卫生—药学]