title: Coordinative Amphiphiles as Tunable siRNA Transporters.
abstract: In this study, we developed coordinative amphiphiles for use as novel siRNA transporters. As a modification of a conventional cationic lipid structure, we replaced the cationic head with zinc(II)-dipicolylamine complex (Zn/DPA) as a phosphate-directing group, and used various membrane-directing groups in the place of the hydrophobic tails. These simple amphiphiles are readily synthesized and easy to modify. The Zn/DPA head groups bind to the phosphate backbones of siRNAs, and to our surprise, they prevented the enzymatic degradation of siRNAs by RNase A. Interestingly, the Zn/DPA head itself exhibited moderate transfection efficiency, and its combination with a membrane-directing group-oleoyl (CA1), pyrenebutyryl (CA2), or biotin (CA3)-enhanced the delivery efficiency without imparting significant cytotoxicity. Notably, the uptake pathway was tunable depending on the nature of the membrane-directing group. CA1 delivered siRNAs mainly through caveolae-mediated endocytosis, and CA2 through clathrin- and caveolin-independent endocytosis; CA3 recruited siRNAs specifically into biotin receptor-positive HepG2 cells through receptor-mediated endocytosis. Thus, it appears possible to develop tunable siRNA transporters simply by changing the membrane-directing parts. These are the first examples of amphiphilic siRNA transporters accompanying coordinative interactions between the amphiphiles and siRNAs.
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology , 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea.
authors.forename: Jin Bum
authors.initials: JB
authors.lastname: Kim
authors.affiliation: Center for Self-Assembly and Complexity, Institute for Basic Science (IBS), and Department of Chemistry, Pohang University of Science and Technology , 77 Cheongam-ro, Nam-gu, Pohang 37673, Republic of Korea.
authors.forename: Yeong Mi
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Graduate School of Analytical Science and Technology, Chungnam National University , 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Republic of Korea.
authors.forename: Jooyeon
authors.initials: J
authors.lastname: Ryu
authors.affiliation: Graduate School of Analytical Science and Technology, Chungnam National University , 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Republic of Korea.
authors.forename: Eunji
authors.initials: E
authors.lastname: Lee
authors.affiliation: Center for Self-Assembly and Complexity, Institute for Basic Science (IBS), and Department of Chemistry, Pohang University of Science and Technology , 77 Cheongam-ro, Nam-gu, Pohang 37673, Republic of Korea.
authors.forename: Won Jong
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology , 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea.
authors.forename: Gyochang
authors.initials: G
authors.lastname: Keum
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology , 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea.
authors.forename: Eun-Kyoung
authors.initials: EK
authors.lastname: Bang
mesh_terms: D000588:Amines / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D045325:HCT116 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009942:Organometallic Compounds / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000378:metabolism; D015032:Zinc / Q000737:chemistry
chemical_list: D000588:Amines; D004337:Drug Carriers; D009942:Organometallic Compounds; D010710:Phosphates; D034741:RNA, Small Interfering; D015032:Zinc