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A multichannel nanosensor for instantaneous readout of cancer drug mechanisms

Abstract

Screening methods that use traditional genomic1,2,3, transcriptional4, proteomic5,6 and metabonomic7 signatures to characterize drug mechanisms are known. However, they are time consuming and require specialized equipment. Here, we present a high-throughput multichannel sensor platform that can profile the mechanisms of various chemotherapeutic drugs in minutes. The sensor consists of a gold nanoparticle complexed with three different fluorescent proteins that can sense drug-induced physicochemical changes on cell surfaces8,9,10. In the presence of cells, fluorescent proteins are rapidly displaced from the gold nanoparticle surface and fluorescence is restored. Fluorescence ‘turn on’ of the fluorescent proteins depends on the drug-induced cell surface changes, generating patterns that identify specific mechanisms of cell death induced by drugs. The nanosensor is generalizable to different cell types and does not require processing steps before analysis, offering an effective way to expedite research in drug discovery, toxicology and cell-based sensing.

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Figure 1: Assembly and working principle of the nanosensor.
Figure 2: Workflow for nanosensor-based drug screening.
Figure 3: Screening of chemotherapeutic drug mechanisms using fluorescence fingerprints.
Figure 4: Profiling the mechanisms of drug combinations.

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Acknowledgements

The authors thank D. Joseph Jerry for providing the pTD cell line and C. Stanier for reading the manuscript and providing useful suggestions. This work was supported by National Institutes of Health grant GM077173 and National Science Foundation Center for Hierarchical Manufacturing grant CMMI-1025020.

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Authors and Affiliations

Authors

Contributions

S.R. and V.M.R. conceived the concepts. S.R. designed the experiments. O.R.M. and G.Y. synthesized and characterized the nanoparticle. R.M. and S.R. expressed the fluorescent proteins. S.R., N.L., R.M. and K.S. performed the drug screening studies. S.R., R.M. and N.L. analysed the data, with statistical inputs from C.R. and R.B. S.R. and V.M.R. wrote most of the paper, with contribution from the other authors.

Corresponding author

Correspondence to Vincent M. Rotello.

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The authors declare no competing financial interests.

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Rana, S., Le, N., Mout, R. et al. A multichannel nanosensor for instantaneous readout of cancer drug mechanisms. Nature Nanotech 10, 65–69 (2015). https://doi.org/10.1038/nnano.2014.285

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