Temporal Evolution of the Lipidome Within Biomolecular Coronas on Nanoparticles: A Class‐Dependent Perspective

ABSTRACT To advance a holistic understanding of biomolecular corona that spontaneously forms around engineered nanoparticles (NPs) in biological environments, we investigated the time‐dependent lipidomic variations within the coronas on DNA‐lipoplexes and IgG‐conjugated AuNPs incubated in blood serum. In view of the hydrodynamic size, the formation of in situ corona occurred rapidly upon exposure to serum and continued to expand over the 48‐h incubation period. Whereas hard corona also formed immediately, it appeared to remain largely stable over time. However, untargeted lipidomics mass spectrometry uncovered an evident temporal evolution of the lipidome within the hard coronas. It varied across the different NPs, which notably depended on the respective lipid classes rather than on the structural details of individual molecules. The observed temporal variations in hard corona suggest ongoing molecular exchanges with soft corona throughout the incubation period. Moreover, as exemplified by polyunsaturated phosphatidylethanolamine, chemical transformation, such as lipid peroxidation on the metallic AuNPs, is also an important factor that contributes to the temporal evolution of the lipidome. Considering the limited knowledge of the non‐protein constituents of natural biological coronas, these findings would advance our understanding toward a more comprehensive view of the complete biomolecular corona.