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DNA flowerstructure co-localizes with human pathogens in infected macrophages

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DOI

  • Oskar Franch
  • ,
  • Camino Gutiérrez-Corbo, University of Nuevo Leon
  • ,
  • Bárbara Domínguez-Asenjo, University of Nuevo Leon
  • ,
  • Thomas Boesen
  • Pia Bomholt Jensen
  • Lene N Nejsum
  • Josephine Geertsen Keller
  • Simon Pagaard Nielsen
  • ,
  • Prakruti R Singh, Department of Microbiology and Cell Biology, Indian Institute of Science & Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India
  • ,
  • Rajiv Kumar Jha, Department of Microbiology and Cell Biology, Indian Institute of Science & Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India
  • ,
  • Valakunja Nagaraja, Department of Microbiology and Cell Biology, Indian Institute of Science & Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India
  • ,
  • Rafael Balaña-Fouce, University of Nuevo Leon
  • ,
  • Yi-Ping Ho, Department of Biomedical Engineering, SKS, Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China., e GIOME, Department of Surgery , Prince of Wales Hospital and Chinese University of Hong Kong , Hong Kong , Hong Kong SAR., Centre for Novel Biomaterials , The Chinese University of Hong Kong , Hong Kong SAR , China.
  • ,
  • Rosa María Reguera, University of Nuevo Leon
  • ,
  • Birgitta Ruth Knudsen

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.

Original languageEnglish
JournalNucleic Acids Research
Volume48
Issue11
Pages (from-to)6081-6091
Number of pages11
ISSN0305-1048
DOIs
Publication statusPublished - Jun 2020

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