Metals-organic frameworks (MOFs) have been widely explored in biomedicine, mostly in drug delivery, biosensing, and bioimaging due to their large surface area, tunable porosity, readily chemical functionalization, and good biocompatibility. However, the underlining cellular mechanisms controlling the process for MOF cytotoxicity remains almost completely unknown. Here, we demonstrate that pristine Cu-MOF without any loaded drug selectively inhibited ovarian cancer mainly through promoting tubulin polymerization and destroying the cell actin cytoskeleton (F-actin) to trigger the mitotic catastrophe, accompanying by conventional programmed cell death. To our knowledge, this is the first report claiming that mitotic catastrophe may be an explaining mechanism of MOF cytotoxicity. Cu-MOF with an intrinsic protease-like activity also hydrolyzed cellular cytoskeleton proteins (F-actin). The RNA sequencing data indicated the differential expressional mRNA of cell proliferation and actin cytoskeleton (ACTA2, ACTN3, FSCN2, and SCIN) and mitotic spindles (PLK1 and TPX2) related genes. We found that Cu-MOF as a promising candidate in the disruption of cellular cytoskeleton and the change of the gene expression could be actin altering and antimitotic agents against cancer cells, allowing for fundamental biological and biophysical studies of MOFs.
Keywords: F-actin; MOFs; cells arrest; gene expression; mitotic catastrophe; ovarian cancer cells.