Imperial College London
Alternate

Professor Molly Stevens

Faculty of Engineering, Department of Materials

Professor of Biomedical Materials and Regenerative Medicine
 
 
 
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Contact

 

+44 (0)20 7594 6804m.stevens

 
 
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Location

 

208Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wang:2020:10.1073/pnas.1919749117,
author = {Wang, ST and Gray, MA and Xuan, S and Lin, Y and Byrnes, J and Nguyen, AI and Todorova, N and Stevens, M and Bertozzi, CR and Zuckermann, RN and Gang, O},
doi = {10.1073/pnas.1919749117},
journal = {Proceedings of the National Academy of Sciences of USA},
pages = {6339--6348},
title = {DNA origami protection and molecular interfacing through engineered sequence-defined peptoids},
url = {http://dx.doi.org/10.1073/pnas.1919749117},
volume = {117},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - DNA nanotechnology has established approaches for designing programmable and precisely controlled nanoscale architectures through specific Watson−Crick base-pairing, molecular plasticity, and intermolecular connectivity. In particular, superior control over DNA origami structures could be beneficial for biomedical applications, including biosensing, in vivo imaging, and drug and gene delivery. However, protecting DNA origami structures in complex biological fluids while preserving their structural characteristics remains a major challenge for enabling these applications. Here, we developed a class of structurally well-defined peptoids to protect DNA origamis in ionic and bioactive conditions and systematically explored the effects of peptoid architecture and sequence dependency on DNA origami stability. The applicability of this approach for drug delivery, bioimaging, and cell targeting was also demonstrated. A series of peptoids (PE1–9) with two types of architectures, termed as “brush” and “block,” were built from positively charged monomers and neutral oligo-ethyleneoxy monomers, where certain designs were found to greatly enhance the stability of DNA origami. Through experimental and molecular dynamics studies, we demonstrated the role of sequence-dependent electrostatic interactions of peptoids with the DNA backbone. We showed that octahedral DNA origamis coated with peptoid (PE2) can be used as carriers for anticancer drug and protein, where the peptoid modulated the rate of drug release and prolonged protein stability against proteolytic hydrolysis. Finally, we synthesized two alkyne-modified peptoids (PE8 and PE9), conjugated with fluorophore and antibody, to make stable DNA origamis with imaging and cell-targeting capabilities. Our results demonstrate an approach toward functional and physiologically stable DNA origami for biomedical applications.
AU  - Wang,ST
AU  - Gray,MA
AU  - Xuan,S
AU  - Lin,Y
AU  - Byrnes,J
AU  - Nguyen,AI
AU  - Todorova,N
AU  - Stevens,M
AU  - Bertozzi,CR
AU  - Zuckermann,RN
AU  - Gang,O
DO  - 10.1073/pnas.1919749117
EP  - 6348
PY  - 2020///
SN  - 0027-8424
SP  - 6339
TI  - DNA origami protection and molecular interfacing through engineered sequence-defined peptoids
T2  - Proceedings of the National Academy of Sciences of USA
UR  - http://dx.doi.org/10.1073/pnas.1919749117
UR  - https://www.pnas.org/content/117/12/6339
UR  - http://hdl.handle.net/10044/1/77656
VL  - 117
ER  -
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