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bioRxiv · 10.1101/2023.07.24.550304

Single-cell precision nanotechnology in vivo

MOLBAY, M.·Kick, B.·Zhao, S.·Todorov, M. I.·Ohn, T.-L.·Roth, S.·Simats, A.·Singh, V.·Khalin, I.·Pan, C.·Singh Bhatia, H.·Hellal, F.·Zeidler, R.·Liesz, A.·Plesnila, N.·Dietz, H.·Erturk, A.
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Abstract

Targeting nanoparticle therapeutics with cellular accuracy in whole organisms could open breakthrough opportunities in precision medicine. However, evaluating and fine-tuning the biodistribution of such systems in the whole organism at the cellular level remains a major obstacle. Here, we constructed targetable DNA origami, and analyzed biodistribution in transparent mice, in addition to studying tolerability, clearance kinetics, and immune response parameters. Untargeted DNA origami primarily accumulated in the spleen and the liver, while an immune cell-targeting variant successfully attached to immune cells throughout the body. A cancer cell-targeting mimetic co-localized on solid-tumor metastasis in the liver and the lung. These findings indicate that DNA origami can be directed in vivo, providing an important proof-of-concept and highlights the potential of high-resolution tissue-clearing imaging technologies in their development. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=121 SRC="FIGDIR/small/550304v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@ce216borg.highwire.dtl.DTLVardef@f40bb4org.highwire.dtl.DTLVardef@2c6a66org.highwire.dtl.DTLVardef@1fd7fde_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIThis study demonstrates the potential of DNA origami-based drug delivery systems as versatile tool for for targeted delivery, which could be used to treat a range of diseases with applications. C_LIO_LIThe immune compatibility, half-life, targeting efficiency, and the biodistribution evaluation of DNA origami indicate its potential for systemic drug delivery. C_LIO_LIOur approach enables the assessment of biodistribution of nanoparticles in the intact body with a sensitivity to the single-cell level, highlighting the high-resolution tissue clearing technoloies in revealing DNA origamis feasibility for drug targeting. C_LI

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MOLBAY, M., Kick, B., Zhao, S., Todorov, M. I., Ohn, T.-L., Roth, S., Simats, A., Singh, V., Khalin, I., Pan, C., Singh Bhatia, H., Hellal, F., Zeidler, R., Liesz, A., Plesnila, N., Dietz, H., Erturk, A.. 2023-07-26. Single-cell precision nanotechnology in vivo. https://doi.org/10.1101/2023.07.24.550304

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