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Tuning Autophagy-inducing Activity and Toxicity for Lanthanide Nanocrystals Through Specific Surface-coating Peptide

Author: ZhangYunJiao
Tutor: WenLongPing
School: University of Science and Technology of China
Course: Biochemistry and Molecular Biology
Keywords: autophagy lanthanide (LN) nanocrystals phage display peptides upconversion toxicity cell interaction diagnostic therapeutic
CLC: TB383
Type: PhD thesis
Year: 2012
Downloads: 130
Quote: 0
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Abstract


Induction of autophagy, a critical cellular degradation process, has been observed upon exposure of cells to a variety of nanoparticles and represents both a safety concern and an application niche for engineered nanomaterials. Ability to control the autophagy-inducing activity for these materials and devices is highly desirable and may conceivably be achieved through modulating material-cell interaction. Here, we present a simple yet highly effective solution by surface engineering with non-covalent binding peptides. A short synthetic peptide RE-1, identified via a modified phage display approach, binds to lanthanide (LN) oxide and upconversion nanocrystals with high affinity in a sequence-specific manner, forms a stable coating layer on the surface of the nanoparticles, and effectively abrogates their autophagy-inducing activity. Furthermore, RE-1effectively abrogates the autophagy-inducing activity and toxicity for these nanocrystals through reducing sedimentation and cell interaction of nanoparticles, while RE-1peptide variants with specific amino acid changes exhibit differentially-reduced binding capability, and correspondingly, varied ability to reduce cell interaction and autophagic response. On the other hand, addition of an arginine-glycine-aspartic acid (RGD) motif onto RE-1creates a bi-functional coating peptide that enhances cell interaction and autophagic response for LN upconversion nanocrystals through interacting with integrins. RE-1and its variants provide a versatile tool for tuning cell interaction to achieve the desired level of the autophagic response and may prove useful for the various diagnostic and therapeutic applications of LN-based nanomaterials and nanodevices.

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