Auricularia auriculajudae polysaccharide-cisplatin complexes conjugated with folic acid as new tumor targeting agents

The Auricularia auriculajudae polysaccharide-cisplatin complex (AAP-CDDP) was synthesized and characterized. The drug release, hemocompatibility, anti-tumor activity, and targeting ability of the complex were studied. The results of cell assay showed that the FA-AAP-CDDP complex showed better anti-tumor activity (IC50 lower 49.5%), and displayed higher uptake rate (higher 2-11-fold) than the AAP-CDDP complex. In vivo experiments showed that the FA-AAP-CDDP complex had the same ability as free cisplatin to decrease subcutaneous tumor growth and reduce the level of serum tumor markers in nude mice. Meanwhile, western blotting analysis showed that the FA-AAP-CDDP complex induced apoptosis by activating Bax, Cytochrome-c, and Caspase-3, and down-regulating Bcl-2, which suggested that the FA-AAP-CDDP complex may induce apoptosis through the endogenetic-mitochondrion signaling apoptosis pathways and intrinsic apoptotic pathways. In addition, the organ weights of FA-AAP-CDDP complex treated mice were significant higher than the cisplatin; and these mice had higher superoxide dismutase, catalase, and glutathione peroxidase activities, and less malondialdehyde in the serum. Thus, the FA-AAP-CDDP complex seems to be an effective, potential, and clinically feasible tumor cell-targeted preparation which shows a better clinical efficacy in treatment of cervical cancer, with improved quality of life, immune function and survival rate. (C) 2018 Published by Elsevier B.V.