Hidetoshi Arima
Kumamoto University, Japan
Title: Potential Therapeutic Application of Dendrimer/Cyclodextrin Conjugates with Targeting Ligands as Advanced Carriers for Gene and Oligonucleotides Drugs
Biography
Biography: Hidetoshi Arima
Abstract
So far, we have reported that gene, shRNA and siRNA transfer activity of PAMAM dendrimers (G2-G4) was strikingly increased by conjugation with -cyclodextrin (-CyD) through both an increace in the endosomal escaping effect and a decreasing in cytotoxicity of the dendrimers. However, the PAMAM dendrimer conjugates with -CyD (-CDEs) have no cell-selective gene and oligonucleotides transfer activity. Therefore, we have recently prepared various -CDEs having targeting ligands such as folate, lactose and mannose/fucose as nonviral vectors to delivery DNA, shRNA, siRNA, miRNA and decoy DNA to tumor cells, hepatocytes and Kupffer cells, respectively, since they possess cell-selective entry, endosomal escaping ability, serum resistance and high safe profile. Most recently, we demonstrated that 2PAMAM dendrimer (G3) conjugates with glucuronylglucosyl-β-cyclodextrin (GUG--CDE (G3)) provided superior properties to -CDE (G3). Also, we fairly recently found that sacran, a megamolecular polysaccharide derived from Aphanothece sacrum, enhanced cellular uptake and the RNAi effect of siRNA complexes with -CDEs via a formation of ternary complexes. I will introduce the recent progress of -CDEs and GUG-- CDEs as cell-selective nonviral vectors.