Hematotoxicity of Fe- and Cr-based metal-organic framework nanoparticles in rockfish Sebastes schlegelii

Materials Institute Lavoisier frameworks (MILs), a prominent class of metal-organic frameworks, have garnered significant attention for their potential environmental applications. However, a critical knowledge gap exists regarding their interaction with blood circulatory system and their potential hematotoxicity, which hinders their broader, safe deployment. Herein, we present the first comparative study investigating the hematotoxicity and underlying mechanisms of two representative MIL particles in rockfish (Sebastes schlegelii). Cr-MIL (MIL-101(Cr)-NH₂) induced significant hemolysis of rockfish red blood cells (RBCs), whereas Fe-MIL (MIL-88B(Fe)-NH₂) was hemocompatible. The cytotoxicity caused by Cr-MIL was attributed to its direct interaction with RBCs, resulting in phosphatidylserine externalization, cell membrane injury, generation of free radicals, and calcium influx. Cr-MIL particles attached to the surface of RBCs and were also internalized. Internalized Cr-MIL particles preferentially bound to a unique set of proteins including hydrophobic, higher flexibility, middle molecular weight, and acidic proteins. These findings reveal the detailed mechanisms of MILs' hematological effects, offering a mechanistic foundation for predicting and mitigating their potential hematotoxicity, therefore facilitating their safer environmental application.