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DNA assembly of nanoparticle superstructures for controlled biological delivery and elimination

Abstract

The assembly of nanomaterials using DNA can produce complex nanostructures, but the biological applications of these structures remain unexplored. Here, we describe the use of DNA to control the biological delivery and elimination of inorganic nanoparticles by organizing them into colloidal superstructures. The individual nanoparticles serve as building blocks, whose size, surface chemistry and assembly architecture dictate the overall superstructure design. These superstructures interact with cells and tissues as a function of their design, but subsequently degrade into building blocks that can escape biological sequestration. We demonstrate that this strategy reduces nanoparticle retention by macrophages and improves their in vivo tumour accumulation and whole-body elimination. Superstructures can be further functionalized to carry and protect imaging or therapeutic agents against enzymatic degradation. These results suggest a different strategy to engineer nanostructure interactions with biological systems and highlight new directions in the design of biodegradable and multifunctional nanomedicine.

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Figure 1: Design of nanoparticle superstructures using DNA assembly.
Figure 2: Characterization of core–satellite superstructures.
Figure 3: Macrophage uptake of superstructures as a function of design.
Figure 4: Intracellular processing of superstructures by J774A.1 macrophages.
Figure 5: Renal elimination and tumour accumulation of superstructures.

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Acknowledgements

This research was funded by the Canadian Institute of Health Research (MOP-93532, COP-126588, RMF-111623), the Natural Sciences and Engineering Research Council (NSERC, RGPIN-288231), the Collaborative Health Research Program (CPG-104290, CHRPJ385829), the Canadian Foundation for Innovation and the Ontario Ministry of Research and Innovation. L.Y.T.C. thanks the Canadian Breast Cancer Foundation for a fellowship, and L.Y.T.C. and K.Z. acknowledge NSERC for a fellowship. The authors thank C. Lo and Q. Dai for assistance with animal blood collection, the Advanced Bioimaging Centre at Mt Sinai Hospital, Toronto, Canada, for the use of the TEM, and the ANALEST facility in the Department of Chemistry, University of Toronto, for the use of ICP-AES.

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W.C.W.C., L.Y.T.C. and K.Z. conceived the idea. W.C.W.C and L.Y.T.C. wrote the paper. L.Y.T.C. and K.Z. performed experiments. All authors analysed data.

Corresponding author

Correspondence to Warren C. W. Chan.

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The authors declare no competing financial interests.

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Chou, L., Zagorovsky, K. & Chan, W. DNA assembly of nanoparticle superstructures for controlled biological delivery and elimination. Nature Nanotech 9, 148–155 (2014). https://doi.org/10.1038/nnano.2013.309

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