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

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.

Titania‐Coated Gold Nano‐Bipyramids for Blocking Autophagy Flux and Sensitizing Cancer Cells to Proteasome Inhibitor‐Induced Death

“…First, the effects of the above synthesized NBPs with various surface coatings on autophagy were compared, as the surface chemistry of nanomaterials plays a vital role in their autophagy regulation function 12, 13. Among the four coated NBP samples, only the NBP/TiO 2 nanostructure induced dramatic increases in GFP‐LC3 puncta (Figure 1d) and LC3‐II expression (Figure 1e).…”

“…There has been growing interest in nanomaterials for autophagy regulation. Quantum dots,11 carbon nanotubes,12 lanthanide oxide,13 cerium oxide,14 titanium dioxide (TiO 2 ),15 and silver nanoparticles16 have been identified as autophagy inducers. However, nanomaterials for autophagy inhibition applications are still rare.…”

“…The surface coatings and sizes of nanomaterials are believed to influence their effects on autophagy 12, 13, 17. Among various nanomaterials, gold nanostructures have the advantage of easy control of the surface coatings and particle sizes 20, 21.…”

Autophagy as new emerging cellular effect of nanomaterials

“…Wen group [71][72][73][74] in University of Science and Technology of China made a series of excellent study on the toxicity of rare earth oxides nanomaterials, mainly focused on their impact on cellular autophagy (Table 3). They found that micromolar equivalent concentration of nano-sized neodymium oxide (Nano Nd 2 O 3 ) could induce autophagy and cell death in non-small cell lung cancer NCI-H460 cells.…”

“…And the autophagic response was dose-and time-dependent [72]. In another study, they investigated three rare earth oxides na- [74] achieved to control the ability of Ln 2 O 3 nanocrystals to induce autophagy via surface-coating peptides. In a screening assay they identified a short peptide RE-1 that could reduce Ln 2 O 3 induced autophagy.…”