bc6b00260_si_001.pdf (1.61 MB)
Coordinative Amphiphiles as Tunable siRNA Transporters
journal contribution
posted on 2016-06-30, 00:00 authored by Jin Bum Kim, Yeong Mi Lee, Jooyeon Ryu, Eunji Lee, Won Jong Kim, Gyochang Keum, Eun-Kyoung BangIn 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
groupoleoyl (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.
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Coordinative Amphiphilestunable siRNA transportersphosphate backbonescoordinative interactionsdelivery efficiencycationic lipid structureTunable siRNA Transportersnovel siRNA transportersuptake pathwayamphiphilic siRNA transporterstransfection efficiencycationic headCA 1CA 2CA 3coordinative amphiphiles
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