Tetraphenylethylene‐Featured Fluorescent Supramolecular Nanoparticles for Intracellular Trafficking of Protein Delivery and Neuroprotection

Abstract The delivery of protein into mammalian cells enables the dissection and manipulation of biological processes; however, this potency is challenged by the lack of an efficient protein delivery tool and a means to monitor its intracellular trafficking. Herein, we report that the hierarchical self‐assembly of tetraphenylethylene (TPE)‐featured metal–organic cages (MOCs) and β‐cyclodextrin‐conjugated polyethylenimine can generate fluorescent supramolecular nanoparticles (FSNPs) to deliver protein into neural cells, a cell line that is hard to transfect using conventional strategy. Further, the aggregation‐induced emission (AIE) of TPE enabled the fluorescent monitoring of cytosolic protein release. It is found that FSNPs can deliver and release protein into cytosol for subcellular targeting as fast as 18 h post‐delivery. Moreover, the delivery of molecular chaperone DJ‐1 using FSNPs activates MAPK/ERK signaling of neural cells to protect cells from oxidative stress.