【摘要】 选用具有良好生物相容性的硫代修饰嵌段核酸为载体,将其非硫代修饰部分设计为靶向MUC-1蛋白的核酸适配体序列,同时在其硫代修饰部分通过硫代磷酸酯基团（Phosphorothioate, PS）接枝修饰四价顺铂前药,制备了两亲性核酸-顺铂前药缀合物MUC-1/^PODNA-b-(^PSDNA-g-Pt),并进一步自组装成类似球形核酸（Spherical nucleic acid, SNA）的含铂靶向纳米药物（MUC-1/Pt-SNAs）.结果表明,该纳米药物递送体系载药率高、形貌稳定、分散性好,能够高效靶向MUC-1蛋白过表达的MCF-7乳腺癌细胞,并在体内外实验中表现出优异的抗肿瘤效果和极低的毒副作用.更多还原

【Abstract】 cis-Platin drugs play a vital role in the clinical treatment of various cancers.However,its poor water solubility,non-targeting capability and severe side effects result in limited antitumor efficacy and greatly impede its clinic practices.To address these challenges,we successfully graft a multitude of Pt（Ⅳ）prodrugs on a diblock DNA that consists of a regular phosphodiester DNA segment with MUC-1 aptamer sequence and a phosphorothioate（PS）ploy T segment.After being modified with iodoacetate moiety,the prodrug can efficiently react with PS groups and grafted onto the backbone of PS segment,resulting in the formation of an MUC-1/^PODNA-b-(^PSDNA-g-Pt)conjugate.Owing to its amphiphilic feature,the obtained DNA-drug conjugate（DDC）could further self-assembled into spherical nucleic acid like nanostructure（MUC-1/Pt-SNAs）to serve as a new drug delivery system.With the presence of MUC-1 aptamer on particle surface,MUC-1/Pt-SNAs can actively target the tumor cells overexpressed MUC-1 proteins and internalize into cells with high efficiency.Together with a high drug loading ratio（39.6%）achieved by simple and convenient conjugation method,the obtained DNA-based targeted delivery system shows substantial antitumor effect and low side effects both in vitro and in vivo.更多还原