Enzyme-Responsive Procarriers Capable of Transporting Chloride Ions across Lipid and Cellular Membranes.

Adopting the concept of procarrier for the first time, we demonstrated the controlled transport of chloride ions across lipid and cellular membranes. Procarriers containing highly hydrophilic appendages were initially inactive due to the lack of their partitioning into lipophilic membranes but were activated to transport chloride ions in the presence of specific enzymes that were able to hydrolyze off the appendages to generate an active carrier under specific conditions. Namely, the procarrier with an ester-bond-linked appendage was most activated by an esterase (PLE) at pH = 7.4, whereas the procarrier with a glycosyl-bond-linked appendage was activated only by a glycosylase (AOG) under slightly acidic conditions (pH = 5.5-6). In addition to controlling chloride transport, hydrophilic appendages greatly increase the water solubility of the procarrier, which may improve the deliverability of a hydrophobic active carrier into a plasma membrane.