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

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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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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).

Author information

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.

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) doi:10.1038/nmat3363

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