期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 12, 页码 6339-6348出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1919749117
关键词
DNA nanotechnology; peptoid; molecular coating
资金
- Center for Functional Nanomaterials
- Molecular Foundry
- Laboratory Directed Research and Development grant
- Office of Science, Office of Basic Energy Sciences, of the US Department of Energy (DOE) [DE-SC0012704, DE-AC02-05CH11231]
- US DOE, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering [DE-SC0008772]
- National Institute of General Medical Sciences [P41 GM111244]
- DOE Office of Biological and Environmental Research [KP1605010]
- NIH [S10 OD012331]
- US DOE, Office of Basic Energy Sciences [DE-SC0012704]
- Australian Government through National Computational Infrastructure Project [e90]
- European Research Council Seventh Framework Programme Consolidator Grant Naturale CG [616417]
- Austrian Science Fund (FWF) [E90] Funding Source: Austrian Science Fund (FWF)
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.
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