Dynamic intracellular exchange of nanomaterials’ protein corona perturbs proteostasis and remodels cell metabolism

作者：Rong Cai, Jiayu Ren, Mengyu Guo, Taotao Wei, Ying Liu, Chunyu Xie, Peng Zhang, Zhiling Guo, Andrew J. Chetwynd, Pu Chun Ke, Iseult Lynch, Chunying Chen · 发表于：Proceedings of the National Academy of Sciences · 年份：2022 · DOI：10.1073/pnas.2200363119 · 被引用次数：133 · 研究领域：Endoplasmic Reticulum Stress and Disease、Autophagy in Disease and Therapy、Heat shock proteins research

The nanomaterial–protein “corona” is a dynamic entity providing a synthetic–natural interface mediating cellular uptake and subcellular distribution of nanomaterials in biological systems. As nanomaterials are central to the safe-by-design of future nanomedicines and the practice of nanosafety, understanding and delineating the biological and toxicological signatures of the ubiquitous nanomaterial–protein corona are precursors to the continued development of nano–bio science and engineering. However, despite well over a decade of extensive research, the dynamics of intracellular release or exchange of the blood protein corona from nanomaterials following their cellular internalization remains unclear, and the biological footprints of the nanoparticle–protein corona traversing cellular compartments are even less well understood. To address this crucial bottleneck, the current work screened evolution of the intracellular protein corona along the endocytotic pathway from blood via lysosomes to cytoplasm in cancer cells. Intercellular proteins, including pyruvate kinase M2 (PKM2), and chaperones, displaced some of the initially adsorbed blood proteins from the nanoparticle surface, which perturbed proteostasis and subsequently incited chaperone-mediated autophagy (CMA) to disrupt the key cellular metabolism pathway, including glycolysis and lipid metabolism. Since proteostasis is key to the sustainability of cell function, its collapse and the resulting CMA overdrive spell subseq...