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Tuning the autophagy-inducing activity of lanthanide-based nanocrystals through specific surface-coating peptides

Nature Materials volume 11, pages 817–826 (2012)Cite this article

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Abstract

The induction of autophagy on exposure of cells to a variety of nanoparticles represents both a safety concern and an application niche for engineered nanomaterials. Here, we show that a short synthetic peptide, RE-1, identified by means of phage display, binds to lanthanide (LN) oxide and upconversion nanocrystals (UCN), forms a stable coating layer on the nanoparticles’ surface, and effectively abrogates their autophagy-inducing activity. Furthermore, RE-1 peptide variants exhibit a differentially reduced binding capability, and correspondingly, a varied ability to reduce the autophagic response. We also show that the addition of an arginine–glycine–aspartic acid (RGD) motif to RE-1 enhances autophagy for LN UCN through the interaction with integrins. RE-1 and its variants provide a versatile tool for tuning material–cell interactions to achieve the desired level of autophagy, and may prove useful for the various diagnostic and therapeutic applications of LN-based nanomaterials and nanodevices.

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Figure 1: Phage display identifies a specific high-affinity binding peptide RE-1 for LN nanomaterials.
Figure 2: RE-1 forms a stable coating layer on the surface of UCN.
Figure 3: RE-1 coating abrogates autophagy induction and toxicity for UCN in HeLa cells.
Figure 4: RE-1 coating abrogates autophagy induction and toxicity for LN UCN in vivo.
Figure 5: Reduction of nanocrystal-surface interaction by RE-1 coating.
Figure 6: Enhancement of cell interaction and autophagy induction by coating with RE-1-RGD.

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Acknowledgements

This work was supported by grants from the Chinese Ministry of Sciences 973 Program (2010CB912804), Natural Science Foundation of China (#30830036, #31170966, #31071211), and the Fundamental Research Funds for the Central Universities (WK2070000008).

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Authors and Affiliations

  1. Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China

    Yunjiao Zhang, Fang Zheng, Tianlong Yang, Wei Zhou, Yun Liu, Na Man, Li Zhang & Long-Ping Wen

  2. Sichuan University, Chengdu, Sichuan 610065, China

    Nan Jin

  3. Division of Bioengineering, Faculty of Engineering, National University of Singapore, 7 Engineering Drive 1, Singapore 117574, Singapore

    Qingqing Dou & Yong Zhang

  4. Department of Materials Physics, Zhejiang Normal University, Jinhua, Zhejiang 321004, China

    Zhengquan Li

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  1. Yunjiao Zhang
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Contributions

Yunjiao Z. and L-P.W. conceived and designed the experiments. Yunjiao Z., F.Z., T.Y., Y.L., W.Z., N.M., L.Z. and N.J. performed the experiments. Q.D., Yong Z. and Z.L. synthesized the UCN nanocrystals. Yunjiao Z. and L-P.W. analysed the data and wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to Long-Ping Wen.

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Zhang, Y., Zheng, F., Yang, T. et al. Tuning the autophagy-inducing activity of lanthanide-based nanocrystals through specific surface-coating peptides. Nature Mater 11, 817–826 (2012). https://doi.org/10.1038/nmat3363

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