Recently, a research team led by Prof. CHEN Chunying from the National Center for Nanoscience and Technology (NCNST) has made important progress in studying the evolution of the "nano-protein corona" during endocytosis and its disturbance to protein homeostasis and cell metabolism. Related research achievement was published in Proceedings of the National Academy of Sciences of the United States of America (2022, 119(23), e2200363119).
When nanoparticles enter the biological system, the biomolecules of the biological fluid quickly bind to the surface of the nanoparticles, in which the "nano-protein corona" formed by interacting with protein molecules in the blood as a starting step has a huge impact on the transport and fate of the nanoparticles, which has aroused a widespread concern in the scientific community. How the formation of the nano-protein corona affects the recognition, transport, distribution, function and biological effects of nanoparticles in the tissues and cells of different barrier systems is a "black box" in the biomedical application of nanomaterials, which not only restricts the delivery efficiency of nanomedicine, but also seriously affects their effectiveness and safety.
An important challenge in this area is the complexity of the nano-protein corona, which is influenced by the diversity of biomolecules in different tissues and organs, as well as physiological and pathological states. At present, there is urgent need of unclear knowledge and unknown mechanism on how the protein composition and structural characteristics of the protein corona evolution with the biological microenvironments.
To solve this problem, the research team has revealed the dynamic evolution pattern of the protein composition of the nano-protein corona in the process of cell transport through the innovative application of multi-dimensional multi-omics (proteomics, metabolomics, lipidomics), intermolecular interactions, and in situ mass spectrometry imaging. Taking gold nanoparticles as the model, the dynamic evolution process of the protein corona from the blood system to the intracellular (blood-lysosomal-cytoplasm) was studied. When the nanoparticles were endocytosed into the lysosome from the blood environment, and then escaped from the lysosome into the cytoplasm, the protein composition on the surface of the nanoparticles will change dramatically, most of which are replaced by intracellular protein molecules, retaining only part of the protein corona components formed in the blood environment. The intracellular evolution of the nano-protein corona subsequently not only disturb the intracellular protein homeostasis (proteostasis), trigger the enrichment of chaperone proteins (HSC70, HSP90) and pyruvate kinase M2 (PKM2) on the surface of the intracellular nano-corona, but also stimulate chaperone mediated autophagy (CMA). And it further affect the cell glycolysis, causing changes in cellular energy metabolism, regulating the metabolic process of cellular lipids.
This study elucidated the evolutionary pattern of nanoparticles in the process of transport from blood to subcellular microenvironment, and discovered the specificity of the intracellular microenvironment of nano-protein corona, which reshapes cell metabolism, providing theoretical support for in-depth understanding of the complex biological effects regulated by nano-bio interface of nanomaterials.
CAI Rong and REN Jiayu are the co-first authors of this paper. Prof. CHEN Chunying from NCNST is the corresponding author. This research was supported by the National Key Research and Development Program, the National Natural Science Foundation of China Innovation Group, the Strategic Priority Research Program of CAS, and Shimadzu China Innovation Center.
Figure. Evolution of the nano-protein corona during cell transport. During transport from the blood-lysosomal-cytoplasm, the exchange of components of the protein corona with intracellular proteins (chaperone proteins, metabolic kinases) triggers an increase in chaperone protein-mediated autophagy (CMA) activity and selectively remodels cell metabolism. (Image by CHEN Chunying et al)
National Center for Nanoscience and Technology (NCNST)