内源性双miRNA触发响应的DNA纳米结构动态自组装用于原位递送siRNA  

Endogenous dual miRNA-triggered dynamic assembly of DNA nanostructures for in-situ dual siRNA delivery

作　　者：钟武坤 黄蕾 林玉红 邢超 卢春华 Wukun Zhong;Lei Huang;Yuhong Lin;Chao Xing;Chunhua Lu(MOE Key Laboratory for Analytical Science of Food Safety and Biology,Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety,State Key Laboratory of Photocatalysis on Energy and Environment,College of Chemistry,Fuzhou University,Fuzhou 350116,China;Institute of Nanobiomaterials and Immunology,School of Life Science,Taizhou University,Taizhou 318000,China;Fujian Key Laboratory of Functional Marine Sensing Materials,Center for Advanced Marine Materials and Smart Sensors,Minjiang University,Fuzhou 350108,China)

机构地区：[1]MOE Key Laboratory for Analytical Science of Food Safety and Biology,Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety,State Key Laboratory of Photocatalysis on Energy and Environment,College of Chemistry,Fuzhou University,Fuzhou 350116,China [2]Institute of Nanobiomaterials and Immunology,School of Life Science,Taizhou University,Taizhou 318000,China [3]Fujian Key Laboratory of Functional Marine Sensing Materials,Center for Advanced Marine Materials and Smart Sensors,Minjiang University,Fuzhou 350108,China

出　　处：《Science China Materials》2023年第7期2938-2946,共9页中国科学（材料科学（英文版）

基　　金：supported by the National Key R&D Program of China(2018YFA0902600);the National Natural Science Foundation of China(22174019);the Natural Science Foundation of Fujian(2020J06036);Fuzhou Science and Technology Innovation and Entrepreneurial Talent Cultivation Program Project(2022-R-002)。

摘　　要：通过多重miRNA触发的原位siRNA递送治疗策略可以有效提高对癌细胞的精确治疗.基于DNA纳米结构的可编程性、特异性分子识别、易于功能化修饰和良好生物相容性的特点,我们设计了一个3D DNA纳米治疗平台,用于实现双miRNA触发响应的siRNA原位递送.这种3D DNA纳米结构(TY1Y2)是由DNA四面体支架、两组Y型DNA(Y1和Y2)和EpCAM核酸适体通过自组装构建而成的.TY1Y2被特异性内化至靶标癌细胞后,能够被两个内源性miRNA(miR-21和miR-122)触发,从而产生强的荧光共振能量转移信号,用于双miRNAs成像.同时,治疗性的siRNA(siSurvivin和siBcl2)也可以通过链置换反应从TY1Y2中产生并进行原位释放,实现癌细胞的协同基因治疗.这种3D DNA纳米结构将内源性生物标记物的特异性成像和治疗性基因的原位递送整合为一个多功能纳米平台,在癌症诊断和治疗方面显示出广阔的应用前景.A theranostic strategy of multiple microRNA(miRNA)-triggered in-situ delivery of small interfering RNA(siRNA)can effectively improve the precise therapy of cancer cells.Benefiting from the advantages of programmability,specific molecular recognition,easy functionalization and marked biocompatibility of DNA nanostructures,we designed a three-dimensional(3D)DNA nano-therapeutic platform for dual miRNA-triggered in-situ delivery of siRNA.The 3D DNA nanostructure(TY1Y2)was constructed based on the self-assembly of a DNA tetrahedra scaffold,two sets of Y-shaped DNA(Y1 and Y2),and EpCAM-aptamer which functionalized as the ligand molecule for the recognition of specific cancer cells.After being specifically internalized into the targeted cancer cells,TY1Y2 was triggered by two endogenous miRNAs(miR-21 and miR-122),resulting in the generation of strong fluorescence resonance energy transfer fluorescent signal for dual miRNAs imaging.Meanwhile,the therapeutic siRNAs(siSurvivin and siBcl2)could also be in-situ generated and released from TY1Y2 through the strand-displacement reactions for the synergistic gene therapy of cancer cells.This 3D DNA nanostructure integrated the specific imaging of endogenous biomarkers and the in-situ delivery of therapeutic genes into the multifunctional nanoplatform,revealing the promising applications for the diagnosis and treatment of cancer.

关 键 词：DNA tetrahedra dynamic assembly MIRNA in-situ delivery cell imaging gene therapy 

分 类 号：TB383.1[一般工业技术—材料科学与工程] R730[医药卫生—肿瘤]