PMID- 26616636
OWN - NLM
STAT- MEDLINE
DCOM- 20161019
LR  - 20161230
IS  - 1526-4602 (Electronic)
IS  - 1525-7797 (Linking)
VI  - 17
IP  - 1
DP  - 2016 Jan 11
TI  - siRNA-Loaded Polyion Complex Micelle Decorated with Charge-Conversional Polymer 
      Tuned to Undergo Stepwise Response to Intra-Tumoral and Intra-Endosomal pHs for 
      Exerting Enhanced RNAi Efficacy.
PG  - 246-55
LID - 10.1021/acs.biomac.5b01334 [doi]
AB  - Small interfering RNA (siRNA) needs an efficient delivery vehicle to reach the 
      cytoplasm of target cells for successful RNA interference (RNAi) therapy. This 
      study aimed to develop an siRNA-loaded polyion complex (PIC) micelle equipped 
      with a smart polymeric shell featuring tumor targetability and endosome 
      escapability for enhanced RNAi activity in cancer cells. To this end, an acidic 
      pH-responsive polypeptide was designed to exert a stepwise change in its charged 
      state from negative to modestly positive and highly positive in response to 
      slightly acidic environment of tumor (pH  approximately 6.7) and further lowered-pH condition 
      of late endosomal compartments (pH  approximately 5.0), respectively, for selective binding to 
      cancer cell surface and subsequent endosome disruption. This polypeptide, termed 
      PAsp(DET-CDM/DBCO), was synthesized by introducing acid-labile carboxydimethyl 
      maleate (CDM) and dibenzylcyclooctyne (DBCO) moieties into a polyaspartamide 
      derivative bearing two-repeated aminoethylene side chains (PAsp(DET)). Then, 
      PAsp(DET-CDM/DBCO) was installed on the surface of disulfide cross-linked PIC 
      micelles prepared from cholesterol-modified siRNA (Chol-siRNA) and 
      azide-poly(ethylene glycol)-b-poly[(3-mercaptopropylamidine)-L-lysine] 
      (N3-PEG-b-PLys(MPA)) through the copper-free click reaction. Successful 
      PAsp(DET-CDM/DBCO) coverage of PIC micelles was confirmed by a significant 
      decrease in zeta-potential as well as a narrowly distributed size of 40 nm. The 
      PAsp(DET-CDM/DBCO)-installed micelles significantly improved the gene-silencing 
      efficiency in cultured lung cancer cells, compared with nonmodified control 
      micelles, especially after incubation at pH 6.7. This improved silencing activity 
      was nicely correlated with the facilitated cellular uptake of siRNA payloads at 
      the acidic pH and the efficient endosomal escape. These results demonstrate that 
      the acidic pH-responsive polypeptide shell is a promising design strategy for 
      tumor-targeted siRNA delivery.
FAU - Tangsangasaksri, Montira
AU  - Tangsangasaksri M
AD  - Department of Bioengineering, Graduate School of Engineering, The University of 
      Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
FAU - Takemoto, Hiroyasu
AU  - Takemoto H
AD  - Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of 
      Technology , R1-11, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan.
FAU - Naito, Mitsuru
AU  - Naito M
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 - Maeda, Yoshinori
AU  - Maeda 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 - Sueyoshi, Daiki
AU  - Sueyoshi D
AD  - Department of Bioengineering, Graduate School of Engineering, The University of 
      Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
FAU - Kim, Hyun Jin
AU  - Kim HJ
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 - Ahn, Jooyeon
AU  - Ahn J
AD  - Department of Materials Engineering, Graduate School of Engineering, The 
      University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
FAU - Azuma, Ryota
AU  - Azuma R
AD  - Department of Materials Engineering, Graduate School of Engineering, The 
      University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
FAU - Nishiyama, Nobuhiro
AU  - Nishiyama N
AD  - Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of 
      Technology , R1-11, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan.
AD  - Innovation Center of NanoMedicine, Institute of Industry Promotion-Kawasaki , 
      3-25-14 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, 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  - Innovation Center of NanoMedicine, Institute of Industry Promotion-Kawasaki , 
      3-25-14 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
FAU - Kataoka, Kazunori
AU  - Kataoka K
AD  - Department of Bioengineering, Graduate School of Engineering, The University of 
      Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
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.
AD  - Innovation Center of NanoMedicine, Institute of Industry Promotion-Kawasaki , 
      3-25-14 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151208
PL  - United States
TA  - Biomacromolecules
JT  - Biomacromolecules
JID - 100892849
RN  - 0 (Micelles)
RN  - 0 (Peptides)
RN  - 0 (Polymers)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Biological Transport
MH  - Cell Line, Tumor
MH  - Click Chemistry/methods
MH  - Endocytosis/physiology
MH  - Genetic Therapy/*methods
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Lung Neoplasms/genetics/metabolism/*therapy
MH  - *Micelles
MH  - Peptides/chemical synthesis/chemistry/*metabolism
MH  - Polymers/chemistry
MH  - RNA Interference
MH  - RNA, Small Interfering/genetics/*metabolism
MH  - Transfection/*methods
EDAT- 2015/12/01 06:00
MHDA- 2016/11/12 06:00
CRDT- 2015/12/01 06:00
PHST- 2015/12/01 06:00 [entrez]
PHST- 2015/12/01 06:00 [pubmed]
PHST- 2016/11/12 06:00 [medline]
AID - 10.1021/acs.biomac.5b01334 [doi]
PST - ppublish
SO  - Biomacromolecules. 2016 Jan 11;17(1):246-55. doi: 10.1021/acs.biomac.5b01334. 
      Epub 2015 Dec 8.