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  Supramolecular aptamer nano-constructs for receptor-mediated targeting and light-triggered release of chemotherapeutics into cancer cells

Prusty, D. K., Adam, V., Zadegan, R. M., Irsen, S., & Famulok, M. (2018). Supramolecular aptamer nano-constructs for receptor-mediated targeting and light-triggered release of chemotherapeutics into cancer cells. Nature Communications, 9: 535. doi:10.1038/s41467-018-02929-2.

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Prusty, Deepak K.1, Author
Adam, Volker2, Author
Zadegan, Reza M.2, Author
Irsen, Stephan3, Author           
Famulok, Michael1, Author           
Affiliations:
1Max Planck Fellow Chemical Biology, Center of Advanced European Studies and Research (caesar), Max Planck Society, Ludwig-Erhard-Allee 2, 53175 Bonn, DE, ou_2173681              
2External Organizations, ou_persistent22              
3Electron Microscopy and Analytics, Center of Advanced European Studies and Research (caesar), Max Planck Society, Ludwig-Erhard-Allee 2, 53175 Bonn, DE, ou_2173680              

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 Abstract: Platforms for targeted drug-delivery must simultaneously exhibit serum stability, efficient directed cell internalization, and triggered drug release. Here, using lipid-mediated self-assembly of aptamers, we combine multiple structural motifs into a single nanoconstruct that targets hepatocyte growth factor receptor (cMet). The nanocarrier consists of lipidated versions of a cMet-binding aptamer and a separate lipidated GC-rich DNA hairpin motif loaded with intercalated doxorubicin. Multiple 2′,6′-dimethylazobenzene moieties are incorporated into the doxorubicin-binding motif to trigger the release of the chemotherapeutics by photoisomerization. The lipidated DNA scaffolds self-assemble into spherical hybrid-nanoconstructs that specifically bind cMet. The combined features of the nanocarriers increase serum nuclease resistance, favor their import into cells presumably mediated by endocytosis, and allow selective photo-release of the chemotherapeutic into the targeted cells. cMet-expressing H1838 tumor cells specifically internalize drug-loaded nanoconstructs, and subsequent UV exposure enhances cell mortality. This modular approach thus paves the way for novel classes of powerful aptamer-based therapeutics.

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Language(s): eng - English
 Dates: 2018-02-07
 Publication Status: Published online
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 Rev. Type: Peer
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Title: Nature Communications
  Abbreviation : Nat Commun
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 9 Sequence Number: 535 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723