Cancer Cells Degrade the Nanoparticle Protein Corona for Biosynthesis

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.