Highly efficient and facile fabrication of monodispersed Au nanoparticles using pullulan and their application as anticancer drug carriers

This work presented a simple, rapid, green and efficient approach to the synthesis of gold nanoparticles using pullulan as a reducing/stabilizing/capping agent for drug delivery systems to increase the safety and efficacy of these systems. Monodispersed AuNPs@pullulan with prolonged stability were fully characterized by UV-VIS, FTIR, TEM, EDX, TGA and zeta potential analyses. A mechanism of AuNPs formation was proposed in which pullulan created reducing species for the reduction of Au³⁺ to AuNPs (Au⁰) that resulted in the formation of spherical AuNPs@pullulan with an average size of approximately 11±5nm, while the hydroxyl groups of pullulan were oxidized to carboxylate compounds. Novel cassiarin A chloride derivatives (3d and 3i) as candidate anticancer drugs were successfully loaded onto AuNPs@pullulan through electrostatic interactions. AuNPs@pullulan-3d (IC₅₀=6.0±0.1μM) and AuNPs@pullulan-3i (5.2±0.1μM) exhibited a 10.2-fold and 7.1-fold higher cytotoxicity against KATO-III cells than free compounds 3d (60.9±0.6μM), 3i (37.1±0.2μM) and cisplatin (64.5±0.9μM), respectively. AuNPs@pullulan exhibited high cellular uptake, biocompatibility and non-cytotoxicity to normal cells. Therefore, AuNPs@pullulan-3d or AuNPs@pullulan-3i have the potential to be developed for treatment of gastric cancer.