Abstract

Investigation of the protein corona of nanoscale metal–organic frameworks (NMOFs) is crucial for their safety assessment; however, it remains inadequately addressed. This study specifically focused on the impact of the bridging linker on the protein corona formation of NMOFs by utilizing nanoscale UiO66/UiO66-NH2 and human serum albumin (HSA) as models. Both UiO66 and UiO66-NH2 effectively quenched the endogenous fluorescence of HSA through a static quenching mechanism. Notably, UiO66 with higher hydrophobicity exhibited a stronger binding affinity (5.62 × 104 L·mol–1) with HSA than the UiO66-NH2–HSA system (2.51 × 104 L·mol–1) at 310 K. UiO66 also adsorbed a greater amount of HSA, induced conformational rearrangement in HSA to a greater extent, and finally led to a significant reduction in the protein surface hydrophobicity. Computer docking and molecular dynamics (MD) simulations further confirmed that HSA demonstrated a higher binding energy, lower total energy, and smaller solvent-accessible surface area when interacting with the bridging linker of UiO66. Moreover, although UiO66 displayed lower cytotoxicity toward 293T cells, UiO66-NH2 exhibited better blood compatibility as evidenced by the elevated values of activated partial thromboplastin time (APTT, 28–57 s) and prothrombin time (PT, 11.7–13.1 s).