Spiropyran-Appended Cucurbit[6]uril Enabling Direct Generation of 2D Materials inside Living Cells.

The unique structural advantage and physicochemical properties render some 2D materials emerging platforms for intracellular bioimaging, biosensing, or disease theranostics. Despite recent advances in this field, one major challenge lies in bypassing the endocytic uptake barrier to allow internalization of very large 2D materials that have longer retention time in cells, and hence greater potency as intracellular functional platforms than small, endocytosable counterparts. Here, an engineered cucurbit[6]uril carrying at its periphery multiple spiropyran pendants that readily translocates into cytosol, and then polymerizes laterally and non-covalently in a controlled manner, enabling direct generation of 2D materials inside living cells, is reported. The resultant 2D materials are single-monomer-thick and can in situ grow up to 0.8-1.2 µm in lateral size, experimentally proved too large to be endocytosed from outside the cells even after surface engineered with biorecognition entities. A Förster resonance energy transfer assay is further devised for real-time visualization of the polymerization dynamics in vivo, clearly demonstrating the rationale in this study. With the otherwise non-endocytosable large 2D materials gaining access to cytosol, potent intracellular signaling or theranostic platform that surpasses the intrinsic performance limit of conventional small counterparts are in sight.