Genistein-loaded nanoparticles of star-shaped diblock copolymer mannitol-core PLGA–TPGS for the treatment of liver cancer

The purpose of this research is to develop nanoparticles (NPs) of star-shaped copolymer mannitol-functionalized PLGA–TPGS for Genistein delivery for liver cancer treatment, and evaluate their therapeutic effects in liver cancer cell line and hepatoma-tumor-bearing nude mice in comparison with the linear PLGA nanoparticles and PLGA–TPGS nanoparticles. The Genistein-loaded M-PLGA–TPGS nanoparticles (MPTN), prepared by a modified nanoprecipitation method, were observed by FESEM and TEM to be near-spherical shape with narrow size distribution. The nanoparticles were further characterized in terms of their size, size distribution, surface charge, drug-loading content, encapsulation efficiency and in vitro drug release profiles. The data showed that the M-PLGA–TPGS nanoparticles were found to be stable, showing almost no change in particle size and surface charge during 3-month storage of their aqueous solution. In vitro Genistein release from the nanoparticles exhibited biphasic pattern with burst release at the initial 4days and sustained release afterwards. The cellular uptake efficiency of fluorescent M-PLGA–TPGS nanoparticles was 1.25-, 1.22-, and 1.29-fold higher than that of the PLGA–TPGS nanoparticles at the nanoparticle concentrations of 100, 250, and 500μg/mL, respectively. In the MPTN group, the ratio of apoptotic cells increased with the drug dose increased, which exhibited dose-dependent effect and a significant difference compared with Genistein solution group (p