DNA flowerstructure co-localizes with human pathogens in infected macrophages.
DNA
/ analysis
DNA Replication
Fluorescence
Half-Life
Humans
Leishmania infantum
/ metabolism
Leishmaniasis
/ therapy
Macrophages
/ cytology
Mycobacterium tuberculosis
/ metabolism
Nanostructures
/ analysis
Nucleic Acid Amplification Techniques
Phagocytosis
Phagosomes
/ chemistry
Tuberculosis
/ therapy
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
19 06 2020
19 06 2020
Historique:
accepted:
24
04
2020
revised:
16
04
2020
received:
30
10
2019
pubmed:
14
5
2020
medline:
9
9
2020
entrez:
14
5
2020
Statut:
ppublish
Résumé
Herein, we characterize the cellular uptake of a DNA structure generated by rolling circle DNA amplification. The structure, termed nanoflower, was fluorescently labeled by incorporation of ATTO488-dUTP allowing the intracellular localization to be followed. The nanoflower had a hydrodynamic diameter of approximately 300 nanometer and was non-toxic for all mammalian cell lines tested. It was internalized specifically by mammalian macrophages by phagocytosis within a few hours resulting in specific compartmentalization in phagolysosomes. Maximum uptake was observed after eight hours and the nanoflower remained stable in the phagolysosomes with a half-life of 12 h. Interestingly, the nanoflower co-localized with both Mycobacterium tuberculosis and Leishmania infantum within infected macrophages although these pathogens escape lysosomal degradation by affecting the phagocytotic pathway in very different manners. These results suggest an intriguing and overlooked potential application of DNA structures in targeted treatment of infectious diseases such as tuberculosis and leishmaniasis that are caused by pathogens that escape the human immune system by modifying macrophage biology.
Identifiants
pubmed: 32402089
pii: 5836771
doi: 10.1093/nar/gkaa341
pmc: PMC7293011
doi:
Substances chimiques
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6081-6091Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
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