A near-infrared naphthalimide fluorescent probe for targeting the lysosomes of liver cancer cells and specifically selecting HSA

Human serum albumin (HSA) plays a pivotal role in various physiological processes of humans, and is generally considered to be one of the early signs of many diseases. Although dysfunction of intracellular lysosome is accompanied in those diseases, the regulation mechanism of HSA in lysosomes still need to be explored. In this work, we report a novel near-infrared naphthalimide probe NI-1 that specifically detects HSA in intracellular lysosomes with the "turn-on" fluorescent sensing modes. In the cell, the N-containing malononitrile group of NI-1 could bind to the lysosome. Moreover, NI-1 can specifically enter the site II hydrophobic cavity of HSA in lysosome. Due to the binding force between NI-1 and HSA, strong steric hindrance and the hydrophobic pocket inside HSA inhibit the twisted internal charge transfer (TICT) effect in the probe itself. Therefore, NI-1 emits strong red fluorescence. More importantly, NI-1 can effectively localize bioimaging of exogenous and endogenous HSA in lysosome. In addition, the novel probe NI-1 achieved a much high selectivity for HSA over bovine serum albumin (BSA), and the interaction mechanism between probe NI-1 and HSA or BSA site II was explained for the first time through molecular docking methods. These results indicate that the probe NI-1 has great potential in exploring further function of HSA for pharmacy and medicine.