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Recognition-mediated activation of therapeutic gold nanoparticles inside living cells

Nature Chemistry volume 2, pages 962–966 (2010)Cite this article

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Abstract

Supramolecular chemistry provides a versatile tool for the organization of molecular systems into functional structures and the actuation of these assemblies for applications through the reversible association between complementary components. Use of this methodology in living systems, however, represents a significant challenge owing to the chemical complexity of cellular environments and lack of selectivity of conventional supramolecular interactions. Herein, we present a host–guest system featuring diaminohexane-terminated gold nanoparticles (AuNP–NH2) and complementary cucurbit[7]uril (CB[7]). In this system, threading of CB[7] on the particle surface reduces the cytotoxicity of AuNP–NH2 through sequestration of the particle in endosomes. Intracellular triggering of the therapeutic effect of AuNP–NH2 was then achieved through the administration of 1-adamantylamine (ADA), removing CB[7] from the nanoparticle surface, causing the endosomal release and concomitant in situ cytotoxicity of AuNP–NH2. This supramolecular strategy for intracellular activation provides a new tool for potential therapeutic applications.

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Figure 1: Schematic of the gold nanoparticle and surface groups, and the use of intracellular host–guest complexation to trigger nanoparticle cytotoxicity.
Figure 2: NMR titration and TEM of AuNP–NH2–CB[7] complex.
Figure 3: Cellular uptake of gold nanoparticles.
Figure 4: Intracellular localization of gold nanoparticles.
Figure 5: Cytotoxicity of AuNP–NH2 and AuNP–NH2–CB[7] and modulating cytotoxicity of the gold nanoparticles.

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Acknowledgements

The authors thank D. Solfiell for his assistance in preparing this manuscript. S.S.A. acknowledges a graduate school fellowship. This work was supported by the National Institites of Health (GM077173, V.M.R.), and L.I. thanks the National Science Foundation (CHE-0615049 and CHE-0914745) for financial support.

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  1. Chaekyu Kim and Sarit S. Agasti: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Chemistry, University of Massachusetts, 710 North Pleasant Street, Amherst, 01003, Massachusetts, USA

    Chaekyu Kim, Sarit S. Agasti, Zhengjiang Zhu & Vincent M. Rotello

  2. Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland, 20742, USA

    Lyle Isaacs

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Contributions

C.K., S.S.A., L.I. and V.M.R. conceived and designed the experiments. C.K., S.S.A. and Z.Z. performed the experiments. C.K., S.S.A., Z.Z., L.I. and V.M.R. analysed the data and wrote the paper.

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Correspondence to Vincent M. Rotello.

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Kim, C., Agasti, S., Zhu, Z. et al. Recognition-mediated activation of therapeutic gold nanoparticles inside living cells. Nature Chem 2, 962–966 (2010). https://doi.org/10.1038/nchem.858

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