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

Rong Cai, Jiayu Ren, Mengyu Guo, Taotao Wei, Ying Liu, Chunyu Xie, Peng Zhang, Zhiling Guo, Andy Chetwynd, Iseult Lynch, Pu Chun Ke, Chunying Chen

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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 subsequent cell death and aging. Our findings shed light on the consequences of the transport of extracellular proteins by nanoparticles on cell metabolism.
Original languageEnglish
Article numbere2200363119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number23
Publication statusPublished - 2 Jun 2022


  • cell metabolism
  • chaperone-mediated autophagy
  • protein corona
  • proteostasis

ASJC Scopus subject areas

  • General


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