Figure 2. Schematic illustration for the enhanced hydrolysis of PTX-S-S-VE.

The prodrug will experience a two stepped hydrolysis to overcome the steric hindrance and polarity hurdles. The disulfide bond will be cleaved in tumor cells because the concentration of GSH in tumor cells is much higher than in blood plasma. This initial hydrolysate will then be further hydrolyzed to PTX because of the increased polarity.