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Carbon nanotube-assisted optical activation of TGF-β signalling by near-infrared light

Nature Nanotechnology volume 10, pages 465–471 (2015)Cite this article

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Abstract

Receptor-mediated signal transduction modulates complex cellular behaviours such as cell growth, migration and differentiation. Although photoactivatable proteins have emerged as a powerful tool for controlling molecular interactions and signalling cascades at precise times and spaces using light, many of these light-sensitive proteins are activated by ultraviolent or visible light, which has limited tissue penetration. Here, we report a single-walled carbon nanotube (SWCNT)-assisted approach that enables near-infrared light-triggered activation of transforming growth factor β (TGF-β) signal transduction, an important signalling pathway in embryonic development and cancer progression. The protein complex of TGF-β and its latency-associated peptide is conjugated onto SWCNTs, where TGF-β is inactive. Upon near-infrared irradiation, TGF-β is released through the photothermal effect of SWCNTs and becomes active. The released TGF-β activates downstream signal transduction in live cells and modulates cellular behaviours. Furthermore, preliminary studies show that the method can be used to mediate TGF-β signalling in living mice.

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Figure 1: Schematic of carbon nanotube-assisted optical activation of TGF-β signalling by NIR light.
Figure 2: NIR-triggered release of active TGF-β1 from SWCNT–SLC in vitro.
Figure 3: Optical activation of TGF-β signalling in live cells.
Figure 4: Optical control of cellular behaviours by NIR light.
Figure 5: NIR activation of SWCNT–SLC in living animals.

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Acknowledgements

This work was supported by the National Basic Research Program of China (973 program; 2012CB917303) and the National Natural Science Foundation of China (nos. 91313301, 21425204 and 91127034).

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Author notes

  1. Ling Liu

    Present address: Present address: Department of Chemistry, Princeton University, Princeton, New Jersey 08540, USA,

  2. Liang Lin and Ling Liu: These authors contributed equally to this work

Authors and Affiliations

  1. Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China

    Liang Lin, Ling Liu, Ran Xie, Wei Lin, He Li, Yaya Li & Xing Chen

  2. School of Life Sciences, Tsinghua University, Beijing, 100084, China

    Bing Zhao & Ye-Guang Chen

  3. Children's Hospital Boston and Department of Biological Chemistry and Molecular Pharmacology, Immune Disease Institute, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Minlong Shi & Timothy A. Springer

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  1. Liang Lin
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Contributions

X.C. conceived the original idea and designed the experiments. L.L. and L.L., assisted by B.Z., R.X., W.L., H.L. and Y.L., performed experiments. M.S., Y.C. and T.A.S. contributed materials. L.L., L.L. and X.C. analysed the data and wrote the manuscript. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Xing Chen.

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The authors declare no competing financial interests.

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Lin, L., Liu, L., Zhao, B. et al. Carbon nanotube-assisted optical activation of TGF-β signalling by near-infrared light. Nature Nanotech 10, 465–471 (2015). https://doi.org/10.1038/nnano.2015.28

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