Intracellularly Self-Assembled 2D Materials Induce Apoptotic Cell Death by Impeding Cytosolic Transport

Using a photochemically isomerizable cucurbit[6]uril derivative as a building block, we succeeded in generating a large number of oversized 2D materials within the cytosol of a living cell via controlled self-assembly. Fluorescence recovery after a photobleaching assay indicated that the resulting 2D material pieces posed discernible hindrance to not only diffusive spreading but also motor-driven motion of intracellular components in the cytosol, which eventually induced apoptotic cell death. Such behavior was seldom observed in previous 2D material-bearing cells prepared by endocytosis, as the total lateral size constituted by the endocytosed 2D materials per cell failed to exceed a threshold level, leading to a tortuosity of transport path inadequate to impede cytosolic transport in an appreciable manner. By varying the initial concentration of the building block, the existence of such a threshold was experimentally demonstrated from the relationship between the flow cytometry side scatter of the treated cells and corresponding cell viability. With the otherwise well-regulated cytosolic transport dynamics of living cells being physically altered, therapeutics with a new mechanism of action that counteracts drug resistance or intracellular platforms that advance our understanding of subcellular pathology of certain intractable diseases are in sight.