Encapsulation and Protection of Ultrathin Two-Dimensional Porous Organic Nanosheets within Biocompatible Metal-Organic Frameworks for Live-Cell Imaging

Despite the rapid development of ultrathin two-dimensional (2D) organic nanosheets, it still remains a challenge to stabilize them and prevent restacking so that they could be used in aqueous environments for biological applications such as live-cell bioimaging. Herein, we report an effective approach to stabilize and protect ultrathin 2D porous organic nanosheets (PONs) by encapsulating them with biocompatible zeolitic imidazolate framework-8 (ZIF-8) for in vitro live-cell imaging. We rationally design and synthesize few-layered 2D PONs named NUS 27-29 containing flexible tetraphenylethylene units as aggregation-induced emission (AIE) molecular rotors. The micrometer-sized freestanding 2D nanosheets of NUS 27-29 with thicknesses of 2-5 nm can be easily obtained by exfoliation from their bulk powders. We demonstrate that these 2D nanosheets can be armored by ZIF-8 crystals grown in situ for inhibition of restacking. Importantly, we find that the dynamics of the AIE molecular rotors of NUS 27-29 can be restricted by noncovalent interactions between the 2D nanosheets and ZIF-8 armor, as proved through experimental studies and theoretical simulations. As a result, the integration of these 2D nanosheets in ZIF-8 leads to highly stable, porous, and fluorescent composites. We further demonstrate that these composites can be employed as biological fluorescent probes for in vitro live-cell imaging. Our strategy shows the first example of transporting hydrophobic 2D organic nanosheets into live cancer cells by encapsulating within biocompatible MOFs, which should facilitate the further development of ultrathin 2D nanomaterials for various biological applications.