Kim, Jin Bum Lee, Yeong Mi Ryu, Jooyeon Lee, Eunji Kim, Won Jong Keum, Gyochang Bang, Eun-Kyoung 2024-01-20T03:34:10Z 2024-01-20T03:34:10Z 2021-09-05 2016-08 1043-1802 https://pubs.kist.re.kr/handle/201004/123824 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. English AMER CHEMICAL SOC CELL-PENETRATING PEPTIDES DELIVERY-SYSTEM GENE DELIVERY PLASMID DNA BILAYER-MEMBRANES IN-VIVO INTRACELLULAR DELIVERY MOLECULAR RECOGNITION MEDIATED ENDOCYTOSIS PROTEIN TRANSDUCTION Coordinative Amphiphiles as Tunable siRNA Transporters Article 10.1021/acs.bioconjchem.6b00260 1 BIOCONJUGATE CHEMISTRY, v.27, no.8, pp.1850 - 1856 BIOCONJUGATE CHEMISTRY 27 8 1850 1856 scie scopus 000381716200011 2-s2.0-84983450676 Biochemical Research Methods Biochemistry & Molecular Biology Chemistry, Multidisciplinary Chemistry, Organic Biochemistry & Molecular Biology Chemistry Article CELL-PENETRATING PEPTIDES DELIVERY-SYSTEM GENE DELIVERY PLASMID DNA BILAYER-MEMBRANES IN-VIVO INTRACELLULAR DELIVERY MOLECULAR RECOGNITION MEDIATED ENDOCYTOSIS PROTEIN TRANSDUCTION coordinative amphiphiles siRNA transporters Zn/DPA membrane-directing groups