Size- and shape-dependent cytotoxicity of nano-sized Zr-based porphyrinic metal-organic frameworks to macrophages

The wide utilization of nano-sized metal-organic frameworks (NMOFs) leads to inevitable health risks to humans. Previous studies on health risks of NMOFs mainly focus on the cytotoxic tests of typical NMOFs，but lack sufficient studies on the effects of physiochemical characteristics of NMOFs on the cytotoxicity and the related mechanisms. Here, four kinds of Zr-based porphyrinic NMOFs (PCNs), including spherical 30, 90, and 180 nm PCN-224 and rod-like 90 nm PCN-222, were taken as a proof of the concept to investigate the effects of the size and shape of NMOFs on the cytotoxicity and related mechanisms to macrophages. The 30 nm spherical PCN-224 induced significant rupture of cell membrane and dissolved in lysosome, leading to the most significant cell necrosis among the studied other nano-sized PCNs. However, other studied PCNs showed insignificant membrane rupture and their dissolution in lysosome. Furthermore, the 90 nm-sized PCN-224 led to much more significant cell necrosis by inducing lysosome damage and inhibiting of autophagy flux than the rod-like 90 nm PCN-222. These findings reveal the size- and shape-dependent cytotoxicity of PCNs and the related mechanisms and are helpful to the assessment of the potential health risks of NMOFs and the safe application of NMOFs.