Synthesis and cytotoxicity evaluation of gold nanoparticles/pullulan derivatives for cancer treatment

Abstract

This study focused on the development of multifunctional gold nanoparticles (AuNPs) using pullulan derivatives as a trifunctional reducing, stabilizing and capping agent for targeted delivery of camptothecin (CPT) or doxorubicin (DOX) in order to enhance their efficacy and reduce side effects. The surface of AuNPs was functionalized to contain 3 beneficial components on pullulan as followed: (i) quat188 as a positive charge to increase cellular uptake and activities, (ii) para-aminobenzoic acid (PABA) as a hydrophobic molecule to enhance biocompatibility, and (iii) folic acid (FA) as a targeting ligand to bind with folate receptor on cancerous cell membranes and enhance intracellular uptake. Facile and green synthesis of spherical AuNPs@FA-PABA-QP as nanocarriers under optimum condition were characterized by various spectroscopic and microscopic techniques with high stability and an average size of 12.6±1.5 nm. The cytotoxicity of CPT-AuNPs@FA-PABA-QP and DOX-AuNPs@FA-PABA-QP were evaluated and found to enhance anticancer activity against Chago-k1 cancer cells of CPT and DOX by approximately 2.80 and 4.82-time comparing with Drug-alone, respectively, whereas they exhibited less toxic to normal cells. The release of both drugs from Drug-AuNPs@FA-PABA-QP in pH 5.0 was higher than pH 7.4, when they were highly taken up into cells by folate receptor-mediated endocytosis. Moreover, CPT-AuNPs@FA-PABA-QP and DOX-AuNPs@FA-PABA-QP increased significantly total-apoptosis (14% and 26%) and then enhanced G0-G1 (11%) and S/G2-M (31%) arrest, inducing cell death, respectively. These results suggested that the novel combinations of CPT-AuNPs@FA-PABA-QP and DOX-AuNPs@FA-PABA-QP as new targeted platforms have the potential to be developed for cancer treatments.