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TitleA DNA robotic switch with regulated autonomous display of cytotoxic ligand nanopatterns.
Journal, issue, pagesNat Nanotechnol, Year 2024
Publish dateJul 1, 2024
AuthorsYang Wang / Igor Baars / Ieva Berzina / Iris Rocamonde-Lago / Boxuan Shen / Yunshi Yang / Marco Lolaico / Janine Waldvogel / Ioanna Smyrlaki / Keying Zhu / Robert A Harris / Björn Högberg /
PubMed AbstractThe clustering of death receptors (DRs) at the membrane leads to apoptosis. With the goal of treating tumours, multivalent molecular tools that initiate this mechanism have been developed. However, ...The clustering of death receptors (DRs) at the membrane leads to apoptosis. With the goal of treating tumours, multivalent molecular tools that initiate this mechanism have been developed. However, DRs are also ubiquitously expressed in healthy tissue. Here we present a stimuli-responsive robotic switch nanodevice that can autonomously and selectively turn on the display of cytotoxic ligand patterns in tumour microenvironments. We demonstrate a switchable DNA origami that normally hides six ligands but displays them as a hexagonal pattern 10 nm in diameter once under higher acidity. This can effectively cluster DRs and trigger apoptosis of human breast cancer cells at pH 6.5 while remaining inert at pH 7.4. When administered to mice bearing human breast cancer xenografts, this nanodevice decreased tumour growth by up to 70%. The data demonstrate the feasibility and opportunities for developing ligand pattern switches as a path for targeted treatment.
External linksNat Nanotechnol / PubMed:38951595
MethodsEM (single particle)
Resolution7.4 Å
Structure data

EMDB-19129: A DNA Robotic Switch with Regulated Autonomous Display of Cytotoxic Ligand Nanopatterns
Method: EM (single particle) / Resolution: 7.4 Å

Source
  • synthetic construct (others)
  • Phage M13mp18 (virus)

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