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Organelle-Specific ...
Organelle-Specific Triggered Release of Immunostimulatory Oligonucleotides from Intrinsically Coordinated DNA-Metal-Organic Frameworks with Soluble Exoskeleton
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Wang, Z. (författare)
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Fu, Y. (författare)
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- Kang, Zhengzhong (författare)
- KTH,Teoretisk kemi och biologi
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Liu, X. (författare)
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Chen, N. (författare)
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Wang, Q. (författare)
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- Tu, Yaoquan (författare)
- KTH,Teoretisk kemi och biologi
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Wang, L. (författare)
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Song, S. (författare)
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Ling, D. (författare)
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Song, H. (författare)
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Kong, X. (författare)
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Fan, C. (författare)
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(creator_code:org_t)
- 2017-10-26
- 2017
- Engelska.
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society. - 0002-7863 .- 1520-5126. ; 139:44, s. 15784-15791
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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 (∼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 further 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Other Basic Medicine (hsv//eng)
Nyckelord
- Biocompatibility
- Calcium compounds
- Crystalline materials
- Medical applications
- Nanoparticles
- Nucleic acids
- Oligonucleotides
- Organometallics
- Acidic environment
- Biomedical applications
- Intracellular delivery
- Metal organic framework
- Metalorganic frameworks (MOFs)
- Spatiotemporal control
- Surface functionalities
- Toll-like receptors
- DNA
- calcium phosphate
- cytosine
- guanosine
- immunostimulating agent
- interleukin 6
- nanoparticle
- oligonucleotide
- phosphate
- toll like receptor 9
- tumor necrosis factor
- zirconium
- acidity
- Article
- carbon nuclear magnetic resonance
- chemical binding
- conformation
- controlled study
- cytokine release
- cytotoxicity
- exoskeleton
- fluorescence spectroscopy
- immunostimulation
- immunotherapy
- interactions with DNA
- RAW 264.7 cell line
- transmission electron microscopy
- upregulation
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Wang, Z.
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Fu, Y.
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Kang, Zhengzhong
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Liu, X.
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Chen, N.
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Wang, Q.
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visa fler...
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Tu, Yaoquan
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Wang, L.
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Song, S.
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Ling, D.
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Song, H.
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Kong, X.
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Fan, C.
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visa färre...
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