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

Abstract

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...

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

“…CB­[6] SP was synthesized according to our previously disclosed procedure, which involved the reaction of perhydroxycucurbit[6]­uril with a propionic acid-appended SP derivative. As previously demonstrated, the product was a mixture containing CB[6] SP with three, five, eight, and nine peripheral SP.…”

“…16 In 2021, we reported how to in situ generate 2D materials within the cytosol of living cells via this strategy, which took advantage of a tiny, exquisitely engineered building block. 17 The building block we used was CB [6] SP , a derivative of macrocyclic cucurbit [6]uril (CB [6]), site-specifically modified at its periphery with several photochromic spiropyrane (SP) moieties. When incubated with living cells under visible light, CB [6] SP remained dormant so that it translocated into living cells easily via endocytosis.…”

“…Recently, a few groups demonstrated that artificial architecture of various shapes ( e.g ., nanofibers and nanoparticles) could be directly generated within living cells via controlled intracellular self-assembly . In 2021, we reported how to in situ generate 2D materials within the cytosol of living cells via this strategy, which took advantage of a tiny, exquisitely engineered building block . The building block we used was CB[6] SP , a derivative of macrocyclic cucurbit[6]­uril (CB[6]), site-specifically modified at its periphery with several photochromic spiropyrane (SP) moieties.…”

Porous Electrospun Films with Reversible Photoresponsive Microenvironmental Humidity Regulation: A Controllable Hydrogen-Bonding Synergistic Effect Exhibited by Acrylic Acid Segments

“…As the most typical photoresponsive organic molecule, spiropyran (SP) and its derivatives have aroused significant research interest due to the rapid isomerization and can be recognized by the naked eye. − The spiropyran molecule is formed by orthogonalizing the indoles and benzopyran through the spirocarbon atom. Under UV light irradiation, the C SP 3 -pyran-O bond of spiropyran compounds is broken, and the colorless spiropyran (SP) is converted into a colored ring-opened merocyanine (MC) structure. − After being exposed to visible light, the C SP 3 -pyran-O bond rebinds that converts the colored merocyanine into a colorless spiropyran. , This reversible isomerization performance can make a transition from the closed nonpolar form (SP form) to the open polar form (MC), which leads to wettability changes on the material surfaces. − …”

Schiff Base Reaction in a Living Cell: In Situ Synthesis of a Hollow Covalent Organic Polymer To Regulate Biological Functions

“…Constructing non-natural macromolecules with prolonged retention inside cells to regulate a variety of physiological activities has attracted tremendous scientific interest. [1][2][3][4][5][6] Although the biosynthesis of peptide polymers, supramolecular self-assemblies and two-dimensional materials has been performed in human cells and living organisms by noncovalent bonding, [7][8][9][10] building larger-sized materials based on covalent bonding remains a significant challenge. Artificial-mediated chemical reactions such as free radical photo-polymerization, [11] halogenalkyne coupling, [12] metalfree azide-alkyne cycloaddition, [13][14][15] metal carbene reaction, [16] aniline coupling, [17] and oxidative polymerization [18] have been applied to control cancer cell fate, to modulate biological functions, and for targeted biological analysis.…”