尺寸可控的球型DNA纳米颗粒构筑策略及其应用  

Construction and Application of Size-controllable Spherical DNA Nanoparticles

作　　者：成佳峰 袁伟 丁雨樵 魏旭南 郁志勇 徐立进[1] 董原辰 Jia-feng Cheng;Wei Yuan;Yu-qiao Ding;Xu-nan Wei;Zhi-yong Yu;Li-jin Xu;Yuan-chen Dong(Department of Chemistry,Renmin University of China,Beijing 100872;Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190;University of Chinese Academy of Sciences,Beijing 100049)

机构地区：[1]中国人民大学化学系,北京100872 [2]中国科学院化学研究所,北京100190 [3]中国科学院大学,北京100049

出　　处：《高分子学报》2023年第3期336-345,共10页Acta Polymerica Sinica

基　　金：中国科学院化学研究所人才基金(基金号C220200704/1);北京市自然科学基金(基金号Z180016);国家自然科学基金(基金号21971248)资助项目。

摘　　要：为探究球型DNA纳米颗粒的尺寸对细胞摄取的影响,提出了一种新型构筑策略,制备了一系列尺寸精准可控的球型DNA纳米颗粒,并进一步揭示了球型DNA纳米颗粒的尺寸与MCF-7细胞内化效率的关系;此外,该策略还可以与框架诱导策略相结合,构筑尺寸可控的磷脂囊泡.该结果为构建新型高效的DNA纳米颗粒载药系统提供了理论参考,为特定尺寸的药物载体设计和开发拓展了思路.During last decades,spherical DNA nanoparticles have been demonstrated as a powerful tool for delivering nucleic acids,small molecular drugs and protein,etc.While the importance of the sizes of such nanoparticles has been recognized in cell uptake efficiency,the investigation in detailed mechanism is still limited owing to the lack of tools to prepare size controllable nanoparticles.Herein,we have developed a strategy to construct spherical DNA nanoparticles(AuNP-Gx)with precise and controllable sizes,through the assembly of DNA modified gold nanoparticles and rigid DNA dendrimers(Y1 and Y2)in a layer-by-layer manner.The rigid DNA dendrimers were firstly assembled through three different single strands DNA.Each dendrimer structure(Y1 and Y2)was designed with the sticky-end segments which can further hybridize with the other Y.Therefore,through stepwise incubation with the gold particle core,different particles could be easily prepared through such only two components.The dynamic light scattering(DLS),agarose gel electrophoresis and transmission electron microscopy(TEM)showed that DNA dendrimers have been assembled around gold nanoparticles layer-by-layer,which indicated the successful preparation of AuNP-Gx with precise and controllable sizes.The prepared AuNPGx nucleic acid nanoparticles were successfully used to reveal the size effect of nucleic acid nanoparticle on the uptake efficiency of MCF-7 cells.From the experimental results,it could be observed that AuNP-G1 and AuNPG0 performed the highest internalization efficiency for MCF-7 cells,while the internalization efficiency of the nanoparticles decreased gradually with the increase of the size.A size-controllable phospholipid vesicle with drug encapsulation and delivery potential was also constructed by using AuNP-Gx of different sizes as the frames and using the Frame-Guided Assembly strategy.Besides,the phospholipid vesicles were easily ingested by MCF-7 cells and showed good biocompatibility.This strategy provides a new tool for the design and development

关 键 词：尺寸可控 球型DNA纳米颗粒 DNA自组装 框架诱导组装 

分 类 号：TB383.1[一般工业技术—材料科学与工程] TQ460.4[化学工程—制药化工]