Enzyme Responsive Peptides for Endocytosis and Targeting Golgi Apparatus

Golgi apparatus (GA) is the hub of intracellular trafficking, but selectively targeting GA by synthetic molecules remains a challenge. Here we show that an unconventional type of peptide, as substrates of enzymes (e.g., alkaline phosphatase, thioesterase), for instantly targeting GA of cells. Preliminary mechanistic studies indicate that the peptides, above or below their critical micelle concentrations, enter cells mainly via caveolin-mediated endocytosis or macropinocytosis, respectively. The peptides, at about 5-10 times of the imaging concentrations, buildup in ER and GA, disrupt protein trafficking, thus lead to cell death via multiple pathways. This work illustrates the first example of an enzyme responsive and redox active molecular platform for targeting GA and controlling cell fates.