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Organelle-Specific Triggered Release of Immunostimulatory Oligonucleotides from Intrinsically Coordinated DNA-Metal-Organic Frameworks with Soluble Exoskeleton
Wang, ZJ; Fu, Y; Kang, ZZ; Liu, XG; Chen, N; Wang, Q; Tu, YQ; Wang, LH; Song, SP; Ling, DS; Song, HY; Kong, XQ; Fan, CH
2017
Source PublicationJOURNAL OF THE AMERICAN CHEMICAL SOCIETY
ISSN0002-7863
Volume139Issue:44Pages:15784-15791
Subtype期刊论文
AbstractDNA 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.
KeywordCalcium-phosphate Nanoparticles Controlled Drug-delivery Cancer-immunotherapy Cellular Uptake Sirna Delivery Nucleic-acids In-vivo Cpg-dna Macropinocytosis Hydroxyapatite
DOI10.1021/jacs.7b07895
WOS KeywordCALCIUM-PHOSPHATE NANOPARTICLES ; CONTROLLED DRUG-DELIVERY ; CANCER-IMMUNOTHERAPY ; CELLULAR UPTAKE ; SIRNA DELIVERY ; NUCLEIC-ACIDS ; IN-VIVO ; CPG-DNA ; MACROPINOCYTOSIS ; HYDROXYAPATITE
Indexed BySCI
Language英语
WOS IDWOS:000415028200040
Citation statistics
Cited Times:28[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.sinap.ac.cn/handle/331007/28763
Collection中科院上海应用物理研究所2011-2018年
Recommended Citation
GB/T 7714
Wang, ZJ,Fu, Y,Kang, ZZ,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, ZJ.,Fu, Y.,Kang, ZZ.,Liu, XG.,Chen, N.,...&Fan, CH.(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, ZJ,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.
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