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Organelle-Specific Triggered Release of Immunostimulatory Oligonucleotides from Intrinsically Coordinated DNA-Metal-Organic Frameworks with Soluble Exoskeleton

文献类型：期刊论文

作者Wang, Zejun2,3; Liu, Xiaoguo2,3; Chen, Nan2,3; Wang, Lihua2,3; Song, Shiping2,3; Fan, Chunhai2,3; Fu, Yao4; Kong, Xueqian4; Kang, Zhengzhong5,6; Wang, Qi5
刊名JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
出版日期2017
卷号139期号:44页码:15784-15791
关键词uveitis protein-protein interaction random walk with restart algorithm
ISSN号0002-7863
DOI10.1021/jacs.7b07895
文献子类Article
英文摘要DNA has proven of high utility to modulate the surface functionality of metal-organic frameworks (MOFs) for various biomedical applications. Nevertheless, current methods for. preparing DNA-MOF nanoparticles rely on either inefficient covalent conjugation or specific modification of oligonucleotides. In this work, we report that unmodified oligonucleotides can be loaded on MOFs with high density (similar to 2500 strands/particle) via intrinsic, multivalent coordination between DNA backbone phosphate and unsaturated zirconium sites on MOFs. More significantly, surface-bound DNA can be efficiently released in either bulk solution or specific organelles in live cells when free phosphate ions are present. As a proof-of-concept for using this novel type of DNA-MOFs in immunotherapy, we prepared a construct of immunostimulatory DNA-MOFs (isMOFs) by intrinsically coordinating cytosine-phosphate-guanosine (CpG) oligonucleotides on biocompatible zirconium MOF nanoparticles, which was farther armed by a protection shell of calcium phosphate (CaP) exoskeleton. We demonstrated that isMOFs exhibited high cellular uptake, organelle specificity, and spatiotemporal control of Toll-like receptors (TLR)-triggered immune responses. When isMOF reached endolysosomes via microtubule-mediated trafficking, the CaP exoskeleton dissolved in the acidic environment and in situ generated free phosphate ions. As a result, CpG was released from. isMOFs and stimulated potent immunostimulation in living macrophage cells. Compared with naked CpG MOF, isMOFs exhibited 83-fold up-regulation in stimulated secretion of cytokines. We thus expect this isMOF design with soluble CaP exoskeleton and an embedded sequential "protect-release" program provides a highly generic approach for intracellular delivery of therapeutic nucleic acids.
学科主题Chemistry
WOS关键词CALCIUM-PHOSPHATE NANOPARTICLES ; CONTROLLED DRUG-DELIVERY ; CANCER-IMMUNOTHERAPY ; CELLULAR UPTAKE ; SIRNA DELIVERY ; NUCLEIC-ACIDS ; IN-VIVO ; CPG-DNA ; MACROPINOCYTOSIS ; HYDROXYAPATITE
语种英语
WOS记录号WOS:000415028200040
出版者AMER CHEMICAL SOC
版本出版稿
源URL[http://202.127.25.144/handle/331004/1069]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmaceut, 866 Yuhangtang Rd, Hangzhou 310058, Zhejiang, Peoples R China;
2.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Appl Phys, Div Phys Biol, Shanghai 201800, Peoples R China;
3.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Appl Phys,CAS Key Lab Interfacial P, Bioimaging Ctr,Shanghai Synchrotron Radiat Facil, Shanghai 201800, Peoples R China;
4.Zhejiang Univ, Dept Chem, Ctr Chem High Performance & Novel Mat, Hangzhou 310027, Zhejiang, Peoples R China;
5.Zhejiang Univ, Dept Chem, Hangzhou 310027, Zhejiang, Peoples R China;
6.KTH Royal Inst Technol, Sch Biotechnol, Div Theoret Chem & Biol, SE-10691 Stockholm, Sweden;
7.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab food safety Res, Shanghai 200031, Peoples R China,
推荐引用方式
GB/T 7714		 Wang, Zejun,Liu, Xiaoguo,Chen, Nan,et al. Organelle-Specific Triggered Release of Immunostimulatory Oligonucleotides from Intrinsically Coordinated DNA-Metal-Organic Frameworks with Soluble Exoskeleton[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2017,139(44):15784-15791.
APA Wang, Zejun.,Liu, Xiaoguo.,Chen, Nan.,Wang, Lihua.,Song, Shiping.,...&,.(2017).Organelle-Specific Triggered Release of Immunostimulatory Oligonucleotides from Intrinsically Coordinated DNA-Metal-Organic Frameworks with Soluble Exoskeleton.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,139(44),15784-15791.
MLA Wang, Zejun,et al."Organelle-Specific Triggered Release of Immunostimulatory Oligonucleotides from Intrinsically Coordinated DNA-Metal-Organic Frameworks with Soluble Exoskeleton".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 139.44(2017):15784-15791.

入库方式： OAI收割

来源：上海营养与健康研究所

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