PMID- 24930854
OWN - NLM
STAT- MEDLINE
DCOM- 20150219
LR  - 20181202
IS  - 1878-5905 (Electronic)
IS  - 0142-9612 (Linking)
VI  - 35
IP  - 27
DP  - 2014 Sep
TI  - Actively-targeted polyion complex micelles stabilized by cholesterol and 
      disulfide cross-linking for systemic delivery of siRNA to solid tumors.
PG  - 7887-95
LID - S0142-9612(14)00598-5 [pii]
LID - 10.1016/j.biomaterials.2014.05.041 [doi]
AB  - For small interfering RNA (siRNA)-based cancer therapies, we report an 
      actively-targeted and stabilized polyion complex micelle designed to improve 
      tumor accumulation and cancer cell uptake of siRNA following systemic 
      administration. Improvement in micelle stability was achieved using two 
      stabilization mechanisms; covalent disulfide cross-linking and non-covalent 
      hydrophobic interactions. The polymer component was designed to provide disulfide 
      cross-linking and cancer cell-targeting cyclic RGD peptide ligands, while 
      cholesterol-modified siRNA (Chol-siRNA) provided additional hydrophobic 
      stabilization to the micelle structure. Dynamic light scattering confirmed 
      formation of nano-sized disulfide cross-linked micelles (<50 nm in diameter) with 
      a narrow size distribution. Improved stability of Chol-siRNA-loaded micelles 
      (Chol-siRNA micelles) was demonstrated by resistance to both the dilution in 
      serum-containing medium and counter polyion exchange with dextran sulfate, 
      compared to control micelles prepared with Chol-free siRNA (Chol-free micelles). 
      Improved stability resulted in prolonged blood circulation time of Chol-siRNA 
      micelles compared to Chol-free micelles. Furthermore, introduction of cRGD 
      ligands onto Chol-siRNA micelles significantly facilitated accumulation of siRNA 
      in a subcutaneous cervical cancer model following systemic administration. 
      Ultimately, systemically administered cRGD/Chol-siRNA micelles exhibited 
      significant gene silencing activity in the tumor, presumably due to their active 
      targeting ability combined with the enhanced stability through both hydrophobic 
      interactions of cholesterol and disulfide cross-linking.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Oe, Yusuke
AU  - Oe Y
AD  - Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, 
      The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
FAU - Christie, R James
AU  - Christie RJ
AD  - Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, 
      The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
FAU - Naito, Mitsuru
AU  - Naito M
AD  - Department of Materials Engineering, Graduate School of Engineering, The 
      University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
FAU - Low, Stewart A
AU  - Low SA
AD  - Department of Materials Engineering, Graduate School of Engineering, The 
      University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
FAU - Fukushima, Shigeto
AU  - Fukushima S
AD  - Department of Materials Engineering, Graduate School of Engineering, The 
      University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
FAU - Toh, Kazuko
AU  - Toh K
AD  - Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, 
      The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
FAU - Miura, Yutaka
AU  - Miura Y
AD  - Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, 
      The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
FAU - Matsumoto, Yu
AU  - Matsumoto Y
AD  - Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, 
      The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
FAU - Nishiyama, Nobuhiro
AU  - Nishiyama N
AD  - Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, 
      The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Polymer 
      Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, 
      R1-11, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan.
FAU - Miyata, Kanjiro
AU  - Miyata K
AD  - Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, 
      The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. 
      Electronic address: miyata@bmw.t.u-tokyo.ac.jp.
FAU - Kataoka, Kazunori
AU  - Kataoka K
AD  - Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, 
      The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; 
      Department of Materials Engineering, Graduate School of Engineering, The 
      University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; Department of 
      Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 
      Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; Center for NanoBio Integration, The 
      University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan. Electronic 
      address: kataoka@bmw.t.u-tokyo.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140613
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
RN  - 0 (Amidines)
RN  - 0 (Cross-Linking Reagents)
RN  - 0 (Disulfides)
RN  - 0 (Ions)
RN  - 0 (Micelles)
RN  - 0 (Oligopeptides)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (RNA, Small Interfering)
RN  - 25104-18-1 (Polylysine)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 78VO7F77PN (arginyl-glycyl-aspartic acid)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Amidines/chemical synthesis/chemistry
MH  - Animals
MH  - Cholesterol/*chemistry
MH  - Cross-Linking Reagents/*chemistry
MH  - Disulfides/*chemistry
MH  - Endocytosis
MH  - Female
MH  - *Gene Transfer Techniques
MH  - HeLa Cells
MH  - Humans
MH  - Ions
MH  - Light
MH  - Mice, Nude
MH  - *Micelles
MH  - Neoplasms/*metabolism/pathology
MH  - Oligopeptides/chemical synthesis/chemistry
MH  - Peptides, Cyclic/chemical synthesis/chemistry
MH  - Polyethylene Glycols/chemical synthesis/chemistry
MH  - Polylysine/chemical synthesis/chemistry
MH  - Proton Magnetic Resonance Spectroscopy
MH  - RNA, Small Interfering/*metabolism
MH  - Scattering, Radiation
OTO - NOTNLM
OT  - Active targeting
OT  - Cholesterol modified siRNA
OT  - Cyclic RGD peptide
OT  - Polyion complex micelle
OT  - siRNA delivery
EDAT- 2014/06/17 06:00
MHDA- 2015/02/20 06:00
CRDT- 2014/06/17 06:00
PHST- 2014/05/13 00:00 [received]
PHST- 2014/05/16 00:00 [accepted]
PHST- 2014/06/17 06:00 [entrez]
PHST- 2014/06/17 06:00 [pubmed]
PHST- 2015/02/20 06:00 [medline]
AID - S0142-9612(14)00598-5 [pii]
AID - 10.1016/j.biomaterials.2014.05.041 [doi]
PST - ppublish
SO  - Biomaterials. 2014 Sep;35(27):7887-95. doi: 10.1016/j.biomaterials.2014.05.041. 
      Epub 2014 Jun 13.