Fabrication of Metal Nuclear Acid Framework to Enable Carrier-Free MNAzyme Self-Delivery for Gastric Cancer Treatment

doi:10.1002/adfm.202406650

科研成果详情

题名	Fabrication of Metal Nuclear Acid Framework to Enable Carrier-Free MNAzyme Self-Delivery for Gastric Cancer Treatment
作者	Ma, Xiaodong 1,2,3; Yan, Jiaqi 3; Zhou, Gongting4,5; Li, Yuanqiang 3; Ran, Meixin 3; Li, Chengcheng 3; Chen, Xiaodong1,2,6; Sun, Weijian1,4,5; Zhang, Hongbo2,3,6,7,8; Shen, Xian1,2,6
发表日期	2024-06-03
发表期刊	ADVANCED FUNCTIONAL MATERIALS 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	Ca2+ homeostasis disruption cancer targeting energy exhaustion metal-nucleic acid frameworks MNAzyme
其他关键词	DNAZYME ; PROLIFERATION ; DEGRADATION ; HYBRIDIZATION ; INHIBITION ; MIGRATION ; DESIGN
摘要	Multi-component deoxyribozymes (MNAzymes) have shown extraordinary potential in precise gene therapy in vitro, however, the in vivo application is limited by complicated delivery systems. Herein, a novel DNA-metal binding mechanism is discovered, and metal-nucleic acid frameworks (MNFs) are built composed of MNAzymes and metal ions, which enable the carrier-free self-delivery of MNAzymes. Metal ions have a high affinity to DNA, however, the binding of metals with DNA at 20-30 base pair long (that normally a MNAzyme has) to form MNF structure is challenged by stringent high-temperature synthesis conditions, poor stability of the products, and lack of targeting capabilities. While, it is discovered that through folding and entanglement of the MNAzyme with an aptamer tail, and prolonging the sequence to 71 base pair, the metal MNAzymes binding is significantly improved and stabilized to MNF structure even at room temperature. Moreover, the aptamer tail also endows MNFs with targeting capabilities. As proof of concept, a carrier-free Ca/MNAzyme delivery system at room temperature, loaded with the model imaging protein BSA-Cy5 is synthesized. This system can effectively target Her-2 positive gastric cancer cells with the Her-2 responsive aptamer tail and initiate dual gene regulation, thereby inducing energy depletion in cancer cells.
资助项目	National Natural Science Foundation of China; Academy of Finland; China Food and Health International Pilot Project - Finnish Ministry of Education and Culture, The Leading Talents in Scientific and Technological Innovation from Zhejiang Provincial Ten Thousand Talents Plan [2019R52021]; Key Research and Development Program of Zhejiang Province [2021C03120]; Key Research and Development Program of Wenzhou [ZY2021003]; National Natural Science Foundation [82272172, 81972261]; Medical Health Science and Technology key Project of Zhejiang Provincial and Ministry Health Commission [WKJ-ZJ-2322]; Wenzhou Basic Public Welfare Research Project [2021Y0056]; [82372145]; [353146]; [347897]; [336355]; [337531]
出版者	WILEY-V C H VERLAG GMBH
ISSN	1616-301X
EISSN	1616-3028
DOI	10.1002/adfm.202406650
页数	16
WOS类目	Chemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied ; Physics, Condensed Matter
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
WOS记录号	WOS:001237608000001
收录类别	SCIE ; EI ; SCOPUS
EI入藏号	20242316204234
EI主题词	DNA
EI分类号	461.2 Biological Materials and Tissue Engineering ; 461.6 Medicine and Pharmacology ; 461.8 Biotechnology ; 461.8.1 Genetic Engineering ; 461.9 Biology ; 531.1 Metallurgy ; 801.2 Biochemistry ; 801.4 Physical Chemistry ; 802.2 Chemical Reactions ; 951 Materials Science
URL	查看原文
SCOPUSEID	2-s2.0-85194933961
通讯作者地址	[Sun, Weijian;Shen, Xian]Wenzhou Med Univ, Affiliated Hosp 1, Dept Gen Surg, Wenzhou 325015, Zhejiang, Peoples R China. ; [Zhang, Hongbo;Shen, Xian]Wenzhou Med Univ, Affiliated Hosp 1, Joint Ctr Translat Med, Wenzhou Key Lab Interdiscipline & Translat Med, Wenzhou 325015, Peoples R China. ; [Zhang, Hongbo]Abo Akad Univ, Fac Sci & Engn, Pharmaceut Sci Lab, Turku 20500, Finland. ; [Sun, Weijian]Wenzhou Med Univ, Affiliated Hosp 2, Dept Gastrointestinal Surg, Wenzhou 325027, Zhejiang, Peoples R China. ; [Sun, Weijian]Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325027, Zhejiang, Peoples R China. ; [Zhang, Hongbo;Shen, Xian]Wenzhou Med Univ, Affiliated Hosp 1, Zhejiang Key Lab Intelligent Canc Biomarker Discov, Wenzhou 325015, Peoples R China. ; [Zhang, Hongbo]Univ Turku, Turku Biosci Ctr, Turku 20500, Finland. ; [Zhang, Hongbo]Abo Akad Univ, Turku 20500, Finland.
Scopus学科分类	Electronic, Optical and Magnetic Materials;Chemistry (all);Biomaterials;Materials Science (all);Condensed Matter Physics;Electrochemistry
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/214614
专题	附属第一医院附属第二医院第二临床医学院、附属第二医院、育英儿童医院附属第二医院_胃肠外科
通讯作者	Sun, Weijian; Zhang, Hongbo; Shen, Xian
作者单位	1.Wenzhou Med Univ, Affiliated Hosp 1, Dept Gen Surg, Wenzhou 325015, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Affiliated Hosp 1, Joint Ctr Translat Med, Wenzhou Key Lab Interdiscipline & Translat Med, Wenzhou 325015, Peoples R China; 3.Abo Akad Univ, Fac Sci & Engn, Pharmaceut Sci Lab, Turku 20500, Finland; 4.Wenzhou Med Univ, Affiliated Hosp 2, Dept Gastrointestinal Surg, Wenzhou 325027, Zhejiang, Peoples R China; 5.Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325027, Zhejiang, Peoples R China; 6.Wenzhou Med Univ, Affiliated Hosp 1, Zhejiang Key Lab Intelligent Canc Biomarker Discov, Wenzhou 325015, Peoples R China; 7.Univ Turku, Turku Biosci Ctr, Turku 20500, Finland; 8.Abo Akad Univ, Turku 20500, Finland
第一作者单位	附属第一医院
通讯作者单位	附属第一医院; 附属第二医院; 第二临床医学院，附属第二医院、育英儿童医院; 胃肠外科
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Ma, Xiaodong,Yan, Jiaqi,Zhou, Gongting,et al. Fabrication of Metal Nuclear Acid Framework to Enable Carrier-Free MNAzyme Self-Delivery for Gastric Cancer Treatment[J]. ADVANCED FUNCTIONAL MATERIALS,2024.
APA	Ma, Xiaodong., Yan, Jiaqi., Zhou, Gongting., Li, Yuanqiang., Ran, Meixin., ... & Shen, Xian. (2024). Fabrication of Metal Nuclear Acid Framework to Enable Carrier-Free MNAzyme Self-Delivery for Gastric Cancer Treatment. ADVANCED FUNCTIONAL MATERIALS.
MLA	Ma, Xiaodong,et al."Fabrication of Metal Nuclear Acid Framework to Enable Carrier-Free MNAzyme Self-Delivery for Gastric Cancer Treatment".ADVANCED FUNCTIONAL MATERIALS (2024).