some 2D materials translocate into living cells via endocytosis, offering a promising platform that enables intracellular bioimaging, [1][2][3] biosensing, [4][5][6] or disease theranostics. [7][8][9][10] Despite encouraging advances in this emerging field, one major challenge lies in managing the trade-off between lateral size of the 2D platform and their cellular uptake. In general, 2D materials with a small lateral dimension are easily taken up by cells but clear fast. One typical example [11] is doxorubicinloaded 2D molybdenum disulfide (MoS 2 ) nanosheets recently reported for synergistic chemo-photothermal cancer therapy. The drug-loaded MoS 2 platform, due to its small lateral size (≈116 nm), could be well internalized by cancer cells, but suffered from exocytosis that compromised the therapeutic effect unless exocytosis inhibitor was added. In comparison, large 2D materials have longer retention time in cells, thus affording greater potency to serve as intracellular functional platforms than small counterparts of the same composition. However, an ultrahigh-aspect-ratio makes the endocytosis of very large 2D materials extremely difficult. [12,13] Having this dilemma in mind, previous researchers had to employ relatively small 2D materials (lateral dimension < 200 nm) as intracellular signaling or theranostic platforms, [2][3][4][5][6][7][8][9][10][11] simply because they were readily endocytosable compared with micrometer-sized counterparts, even though the latter were conceivably more qualifying candidates.Indeed, 2D materials, regardless of chemical composition, can invariably be regarded as an assembly composed of laterally connected areal monomeric units that extend in two orthogonal directions. [14,15] These monomers are typically less than 1 nm in size, thus having no trouble being internalized and enriched inside living cells. Bearing this in mind, we envision unprecedentedly large 2D materials can be directly generated in cell milieu provided that the internalized monomers in situ polymerize efficiently with the inter-monomer connections being strictly confined to lateral directions. As such, the otherwise non-endocytosable large 2D materials can eventually enter the cells, addressing the lateral size versus cellular uptake trade-off aforementioned.An areal monomeric unit designed for such a purpose then must meet several demanding requirements: 1) it should be 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-c...