Polymeric Nanocarriers for Effective Synergistic Action of Sorafenib Tosylate and Gold-sensitized Gamma Radiation Against HepG2 Cells

PURPOSE: One of the key parameters towards effective and synergistic combinatorial anticancer therapeutic models is the nanocarrier. Nearly all previous studies have been limited to one nanocarrier for one drug. However, a comparative study on two polymeric nanocarriers for the same drug against the same cancer cell and under the same conditions helps to rationalize the properties of each polymeric nanocarrier to the effectiveness of the drug-loaded nanocapsules. METHODS: In this study, two of biocompatible polymers, namely poly lactic-co-glycolic acid (PLGA) and polyε-caprolactone (PCL), were used for co-delivery of sorafenib tosylate and gold nanoparticles (G). RESULTS: The anticancer effects of sorafenib tosylate (ST) combined with gold-sensitized radiation therapy were studied and rationalized to the physicochemical properties of each nanocarrier. Both models inhibited the proliferation of HepG2 cells via cell cycle arrest. The use of PCL and PLGA as nanocarriers for the proposed combined (chemo-radio) therapeutic model reduced the viability of HepG2 cells to 26% and 8%, respectively. PCL and PLGA models showed high necrosis levels (15.1 and 16.2, respectively). CONCLUSION: Both PCL and PLGA are good nanocarriers for the proposed combined model. Compared to PCL NPs, PLGA NPs showed enhanced release, higher cytotoxicity and higher necrosis levels.