Article Synopsis
- Clustering of death receptors at the cell membrane can trigger apoptosis, leading to potential cancer treatment through multivalent molecular tools.
- A novel robotic switch nanodevice has been created that selectively activates cytotoxic ligands in acidic tumor microenvironments while remaining inactive in healthy tissue.
- This device, using a switchable DNA origami that reveals ligands in response to lower pH levels, has shown to significantly reduce tumor growth in mice by up to 70%.
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Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11405282 | PMC |
| http://dx.doi.org/10.1038/s41565-024-01676-4 | DOI Listing |
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