The Intracellular Destiny of the Protein Corona: A Study on its Cellular Internalization and Evolution
The Intracellular Destiny of the Protein Corona: A Study on its Cellular Internalization and Evolution
复制标题
DOI：
10.1021/acsnano.6b06411
复制
发表时间：
2016-11-01
期刊：
影响因子：
17.1
通讯作者：
Dawson, Kenneth A.
中科院分区：
文献类型：
--
作者：
Bertoli, Filippo;Garry, David;Dawson, Kenneth A.
已经确定的是，纳米颗粒细胞相互作用的早期阶段至少部分地由蛋白质层和其他生物分子吸附并与周围的生物介质（生物分子冠）缓慢交换来控制。在膜相互作用之后，纳米颗粒通常内化到细胞中并沿着限定的途径运输，例如在许多情况下，内溶酶体途径。事实上，如果原始冠部分保留在纳米颗粒表面上，则该层中的生物分子可能在确定随后的细胞加工中起重要作用。在这项工作中，使用细胞器分离和荧光标记的初始细胞外冠的组合，我们澄清其细胞内的演变为纳米粒子在细胞内旅行。我们发现，存在于原始蛋白质冠中的特定蛋白质保留在纳米颗粒上，直到它们在溶酶体中积累，并且一旦在那里，它们就被降解。我们还报告了不同的裸露表面（氨基和羧基修饰）如何影响这种演变的细节。一个重要的发现是，与从细胞外介质自由运输时观察到的情况相比，相同的血清蛋白质在由纳米颗粒携带到细胞内时可以表现出不同的细胞内加工，作为其冠的组分。
It has been well established that the early stages of nanoparticle cell interactions are governed, at least in part, by the layer of proteins and other biomolecules adsorbed and slowly exchanged with the surrounding biological media (biomolecular corona). Subsequent to membrane interactions, nanoparticles are typically internalized into the cell and trafficked along defined pathways such as, in many cases, the endolysosomal pathway. Indeed, if the original corona is partially retained on the nano particle surface, the biomolecules in this layer may play an important role in determining subsequent cellular processing. In this work, using a combination of organelle separation and fluorescence labeling of the initial extracellular corona, we clarify its intracellular evolution as nanoparticles travel within the cell. We show that specific proteins present in the original protein corona are retained on the nanoparticles until they accumulate in lysosomes, and, once there, they are degraded. We also report on how different bare surfaces (amino and carboxyl modified) affect the details of this evolution. One overarching discovery is that the same serum proteins can exhibit different intracellular processing when carried inside cells by nanoparticles, as components of their corona, compared to what is observed when they are transported freely from the extracellular medium.