PMID- 29250901
OWN - NLM
STAT- MEDLINE
DCOM- 20181221
LR  - 20181221
IS  - 1616-5195 (Electronic)
IS  - 1616-5187 (Linking)
VI  - 18
IP  - 1
DP  - 2018 Jan
TI  - Enhanced Intracellular Delivery of siRNA by Controlling ATP-Responsivity of 
      Phenylboronic Acid-Functionalized Polyion Complex Micelles.
LID - 10.1002/mabi.201700357 [doi]
AB  - Intracellular delivery of small interfering RNA (siRNA) is a long-standing 
      challenge in oligonucleotide therapeutics. Herein, adenosine triphosphate 
      (ATP)-responsive polyion complex micelles assembled from poly(ethylene 
      glycol)-block-poly(l-lysine) (PEG-PLys) bearing 4-carboxy-3-fluorophenylboronic 
      acid (FPBA) moiety in the PLys side chains (FPBA micelle) for the delivery of 
      cholesterol-modified siRNA (Chol-siRNA) are described. The pK(a) of FPBA moiety 
      is 7.2 and, therefore, it exists in equilibrium between negatively charged 
      tetravalent and noncharged hydrophobic trivalent forms in physiological pH 
      conditions. Each form cooperatively stabilizes the micelle in distinct modes, 
      that is, a covalent ester-linkage between charged boronate and ribose 
      functionality at 3' ends of Chol-siRNA and a hydrophobic interaction between 
      noncharged boronic acid and Chol-siRNA. When exposed to ATP at a concentration 
      associated with the intracellular environment, the Chol-siRNA/boronate linkage is 
      readily cleaved to facilitate the release of Chol-siRNA into cytoplasm. In order 
      to further optimize this switching capability, the effect of FPBA modification 
      rate is studied for the resulting ATP-responsive behavior of the micelles. As a 
      result, the range of 23-35% in the modification rate is found suitable to 
      maximize the gene silencing efficiency, demonstrating the potential of the 
      FPBA-modified micelles as ATP-responsive smart siRNA carrier systems.
CI  - (c) 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Naito, Mitsuru
AU  - Naito M
AUID- ORCID: 0000-0002-4237-871X
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 - Yoshinaga, Naoto
AU  - Yoshinaga N
AD  - Department of Bioengineering, Graduate School of Engineering, The University of 
      Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
FAU - Ishii, Takehiko
AU  - Ishii T
AD  - Department of Bioengineering, Graduate School of Engineering, The University of 
      Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
FAU - Matsumoto, Akira
AU  - Matsumoto A
AD  - Kanagawa Institute of Industrial Science and Technology, 2-3-10 Kanda-Surugadai, 
      Chiyoda-ku, Tokyo, 101-0062, Japan.
AD  - Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental 
      University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-0062, Japan.
FAU - Miyahara, Yuji
AU  - Miyahara Y
AD  - Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental 
      University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-0062, 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.
AD  - Department of Materials Engineering, Graduate School of Engineering, The 
      University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
FAU - Kataoka, Kazunori
AU  - Kataoka K
AD  - Innovation Center of NanoMedicine, Kawasaki Institute of Industrial Promotion, 
      3-25-14 Tonomachi, Kawasaki-ku, Kawasaki, 210-0821, Japan.
AD  - Policy Alternatives Research Institute, The University of Tokyo, 7-3-1 Hongo, 
      Bunkyo-ku, Tokyo, 113-0033, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171218
PL  - Germany
TA  - Macromol Biosci
JT  - Macromolecular bioscience
JID - 101135941
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Boronic Acids)
RN  - 0 (Drug Carriers)
RN  - 0 (Micelles)
RN  - 0 (RNA, Small Interfering)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Adenosine Triphosphate/*chemistry
MH  - Anticholesteremic Agents/chemistry/pharmacology
MH  - Boronic Acids/chemistry
MH  - Cellular Microenvironment/drug effects
MH  - Cholesterol/*genetics
MH  - Cytoplasm/drug effects
MH  - Drug Carriers/chemistry/*pharmacology
MH  - Gene Silencing/drug effects
MH  - HeLa Cells
MH  - Humans
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Lysine/chemistry/pharmacology
MH  - Micelles
MH  - Polyethylene Glycols/chemistry/pharmacology
MH  - RNA, Small Interfering/genetics/*pharmacology
OTO - NOTNLM
OT  - ATP-responsivity
OT  - phenylboronic acid
OT  - polyion complex micelles
OT  - siRNA delivery
EDAT- 2017/12/19 06:00
MHDA- 2018/12/24 06:00
CRDT- 2017/12/19 06:00
PHST- 2017/10/27 00:00 [received]
PHST- 2017/11/13 00:00 [revised]
PHST- 2017/12/19 06:00 [pubmed]
PHST- 2018/12/24 06:00 [medline]
PHST- 2017/12/19 06:00 [entrez]
AID - 10.1002/mabi.201700357 [doi]
PST - ppublish
SO  - Macromol Biosci. 2018 Jan;18(1). doi: 10.1002/mabi.201700357. Epub 2017 Dec 18.