2. Academic Validation
  3. Cancer Cells Degrade the Nanoparticle Protein Corona for Biosynthesis

Cancer Cells Degrade the Nanoparticle Protein Corona for Biosynthesis

  • J Am Chem Soc. 2026 Mar 11;148(9):9478-9493. doi: 10.1021/jacs.5c19355.
Qin Ji 1 2 3,  Colin Blackadar 1 2 3,  Atta C Y Chang 1 2 3,  Jamie L Y Wu 4 5 6,  Shrey Sindhwani 7 8 9,  Warren C W Chan 2 10
Affiliations

Affiliations

  • 1 Institute of Biomedical Engineering, University of Toronto, Rosebrugh Building, Toronto, Ontario M5S 3G9, Canada.
  • 2 Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
  • 3 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
  • 4 Innovative Genomics Institute, University of California Berkeley, Berkeley, California 94720, United States.
  • 5 Gladstone Institute of Data Science and Biotechnology, San Francisco, California 94158, United States.
  • 6 Institute for Quantitative Biosciences, Berkeley, California 94720-3220, United States.
  • 7 MD/PhD program, University of Toronto, Medical Science Building, Toronto, Ontario M5S 1A8, Canada.
  • 8 Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 3K3, Canada.
  • 9 Adult Hematology and Medical Oncology Fellowship Program, Section of Hematology/Oncology, University of Chicago, Chicago, Illinois 60637, United States.
  • 10 School of Chemistry, Chemical Engineering, and Biotechnology, Nanyang Technological University, Singapore 637371, Singapore.
PMID: 41739600 DOI: 10.1021/jacs.5c19355
Abstract

Nanoparticles designed to carry medical agents are administered to patients for the detection and treatment of Cancer. Serum proteins form a protein corona on the nanoparticle surface after nanoparticles enter the bloodstream. The protein corona can impact how nanoparticles circulate, interact with, and get taken up by Cancer cells. What happens to the protein corona once inside the cells remains unclear. Here, we discovered that Cancer cells metabolize the protein corona to synthesize new macromolecules. After internalization, nanoparticles and their associated protein corona are trafficked to cell lysosomes. Proteolytic Enzymes degrade the protein corona into Amino acids in the lysosomes. The degraded byproducts are utilized for the synthesis of macromolecules for new cells. The total amount of serum proteins entering cells with the nanoparticles is greater than that in solution. Each internalized 55 nm gold nanoparticle transports an amount of protein equivalent to the uptake of over 250 individual proteins from solution. The uptake of nanoparticles creates an abundance of proteins for cells to carry out biosynthesis. These findings reveal that the nanoparticle protein corona serves as a nutrient reservoir for Cancer cell metabolism.

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