Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
Nat Mater. 2012 Sep;11(9):817-26. doi: 10.1038/nmat3363. Epub 2012 Jul 15.
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.
当细胞暴露于各种纳米粒子时,自噬的诱导既代表了工程纳米材料的安全问题,也代表了其应用领域。在这里,我们表明,通过噬菌体展示鉴定的短合成肽 RE-1 与镧系(LN)氧化物和上转换纳米晶体(UCN)结合,在纳米粒子表面形成稳定的涂层,并有效消除其自噬诱导活性。此外,RE-1 肽变体表现出不同的结合能力降低,相应地,减少自噬反应的能力也不同。我们还表明,通过与整合素相互作用,将精氨酸-甘氨酸-天冬氨酸(RGD)基序添加到 RE-1 中可以增强 LN UCN 的自噬作用。RE-1 及其变体为调节材料-细胞相互作用以达到所需自噬水平提供了一种通用工具,并且可能对基于 LN 的纳米材料和纳米器件的各种诊断和治疗应用有用。