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Nucleic Acids Symposium Series 2005 49(1):17-18; doi:10.1093/nass/49.1.17
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© 2005 Oxford University Press

Smart polymeric micelles as nanocarriers for oligonucleotides and siRNA delivery

Kazunori Kataoka1,2, Keiji Itaka2, Nobuhiro Nishiyama2, Yuichi Yamasaki1, Motoi Oishi3 and Yukio Nagasaki3

1 Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan, 2 Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, 3 Tsukuba Rresearch Center for Interdisciplinary Materials Science, University of Tsukuba, Tsukuba 305-9573, Japan

The development of in vivo delivery systems for oligonucleotides and siRNA is strongly desired to achieve their clinical applications. Recently, polyplex micelles, which are formed through an electrostatic interaction between nucleic acid compounds (DNA and RNA) and poly(ethylene glycol) (PEG)-polycation block copolymers, have received much attention due to their nanometric-scaled size and excellent biocompatibility. Here, three types of newly engineered block copolymers were developed to construct polyplex micelles useful for oligonucleotides and siRNA delivery: (1) PEG-polycation diblock copolymers possessing diamine side-chain with distinctive pKa for siRNA encapsulation into polyplex micelles with high endosomal escaping ability, (2) Lactosylated PEG-(olignucleotide or siRNA) conjugate through acid-labile ß-thiopropionate linkage to construct pH-sensitive PIC micelles, and (3) PEG-poly(methacrylic acid) block copolymer for the construction of organic/inorganic hybrid nanoparticles encapsulating siRNA.


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