Mitochondria-specific delivery methods offer a valuable tool for studying mitochondria-related diseases and provide breakthroughs in therapeutic development. Although several small-molecule and peptide-based transporters have been developed, peptoids, proteolysis-resistant peptidomimetics, are a promising alternative to current approaches. We designed a series of amphipathic peptoids and evaluated their cellular uptake and mitochondrial localization. Two peptoids with cyclohexyl residues demonstrated highly efficient cell penetration and mitochondrial localization without significant adverse effects on the cells and mitochondria. These mitochondria-targeting peptoids could facilitate the selective and robust targeted delivery of bioactive compounds, such as drugs, antioxidants, and photosensitizers, with minimal off-target effects.

We developed a smart activity-based probe that detects the activity of asparaginyl endopeptidase (AEP) in live cells to monitor the dynamics of enzyme regulation. The newly designed probe generated a turn-on fluorescence signal in response to the activity of AEP in living cells without compromising the labelling efficiency or selectivity. Our probe closely reflected the enzyme activity in its native state, detecting subcellular AEP activity in colon cancer cells and neuronal cells.

A dual-mode sensor 1 demonstrated highly specific and sensitive signal changes to multiple analytes based on two distinct mechanisms.