Preparation, physicochemical properties, hemolytic activity and cytotoxicity to cancer cells of polyethylene glycol-Wacao pentacyclic triterpenoid saponin(WPTS-mPEGCOOH)

The low water solubility and high hemolysis rate of Wacao pentacyclic triterpenoid saponin (WPTS) greatly limit its clinical application. It is an urgent problem to increase water solubility and decrease hemolytic activity. It is also an important goal to made it with tumor targeting and enhance its anti-tumor activity. In this study, carboxylated polyethylene glycol (mPEGCOOH) - Wacao pentacyclic triterpenoid saponin (WPTS-mPEGCOOH) was successfully prepared, and the structure was characterized by FT-IR and 1H NMR. The morphology of the conjugate was examined by field emission transmission electron microscopy (FE-TEM). The average particle size of the conjugate was 124.67 ± 3.5 nm and the polydispersity index (PDI) was 0.146 ± 0.012. Polyethylene glycol (PEG) is a kind of hydrophilic polymer. After combining with PEG, the water solubility of the combination was obviously increased. The in vitro release experiment showed that the release of WPTS-mPEGCOOH under acidic conditions (pH 5.0) was greater than that under physiological buffer conditions (pH 7.4). The hemolysis experiment showed that compared with WPTS, WPTS-mPEGCOOH had a lower hemolysis rate at low concentration, but the hemolysis rate was still high at high concentration. In vitro cytotoxicity experiments showed that WPTS and WPTS- mPEGCOOH had good inhibitory effects on MC38 colon cancer cells and HepG2 liver cancer cells, and at the same concentration, WPTS-mPEGCOOH had stronger anticancer effects. Overall, conjugation with PEG increased the water solubility of WPTS, decreased its hemolytic activity, and enhanced its inhibitory effect on cancer cells, which provided a new idea for the development and utilization of Wacao.