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, ZJ; Fu, Y; Kang, ZZ; Liu, XG; Chen, N; Wang, Q; Tu, YQ; Wang, LH; Song, SP; Ling, DS |
| 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 | Calcium-phosphate Nanoparticles Controlled Drug-delivery Cancer-immunotherapy Cellular Uptake Sirna Delivery Nucleic-acids In-vivo Cpg-dna Macropinocytosis Hydroxyapatite |
| ISSN号 | 0002-7863 |
| DOI | 10.1021/jacs.7b07895 |
| 文献子类 | 期刊论文 |
| 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. |
| 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 |
| 源URL | [http://ir.sinap.ac.cn/handle/331007/28763]  |
| 专题 | 上海应用物理研究所_中科院上海应用物理研究所2011-2017年 |
| 推荐引用方式 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. |
入库方式： OAI收割
来源：上海应用物理研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。