PMID- 23480956
OWN - NLM
STAT- MEDLINE
DCOM- 20130827
LR  - 20190115
IS  - 1878-5905 (Electronic)
IS  - 0142-9612 (Linking)
VI  - 34
IP  - 16
DP  - 2013 May
TI  - A pH-responsive cyclodextrin-based hybrid nanosystem as a nonviral vector for 
      gene delivery.
PG  - 4159-4172
LID - S0142-9612(13)00204-4 [pii]
LID - 10.1016/j.biomaterials.2013.02.035 [doi]
AB  - The absence of safe, efficient, cost-effective, and easily scalable delivery 
      platforms is one of the most significant hurdles and critical issues that limit 
      the bench to bedside translation of oligonucleotides-based therapeutics. 
      Acid-labile materials are of special interest in developing nonviral vectors due 
      to their capability of intracellularly delivering therapeutic payload. In this 
      study, a nanovector was designed by integrating a pH-responsive cyclodextrin 
      material and low molecular weight polyethylenimine (PEI). Antisense 
      oligonucleotide (ASON) Bcl-xl could be encapsulated into this hybrid nanosystem 
      with extremely high loading efficiency by a nanoemulsion technique. The developed 
      pH-responsive ASON nanotherapeutics could be efficiently transfected into human 
      lung adenocarcinoma cells in a time- and dose-dependent manner, resulting in 
      effective cell growth inhibition, significant suppression on the expression of 
      Bcl-xl mRNA/protein, and efficient cell apoptosis. Importantly, the new 
      nanovector showed drastically higher efficacy and lower cytotoxicity when 
      compared with PLGA-based counterpart and commonly used cationic vectors like 
      branched PEI (25,000 Da) and Lipofectamine 2000. This pH-responsive hybrid 
      nanosystem may serve as a safe and efficient nonviral vector that may find wide 
      applications in gene therapy.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Chen, Huaping
AU  - Chen H
AD  - Institute of Respiratory Diseases, Xinqiao Hospital of Third Military Medical 
      University, Chongqing 400037, China.
FAU - Liu, Xueping
AU  - Liu X
AD  - Institute of Respiratory Diseases, Xinqiao Hospital of Third Military Medical 
      University, Chongqing 400037, China.
FAU - Dou, Yin
AU  - Dou Y
AD  - Department of Pharmaceutics, College of Pharmacy, Third Military Medical 
      University, Chongqing 400038, China.
FAU - He, Binfeng
AU  - He B
AD  - Institute of Respiratory Diseases, Xinqiao Hospital of Third Military Medical 
      University, Chongqing 400037, China.
FAU - Liu, Li
AU  - Liu L
AD  - Institute of Respiratory Diseases, Xinqiao Hospital of Third Military Medical 
      University, Chongqing 400037, China.
FAU - Wei, Zhenghua
AU  - Wei Z
AD  - Institute of Respiratory Diseases, Xinqiao Hospital of Third Military Medical 
      University, Chongqing 400037, China.
FAU - Li, Jin
AU  - Li J
AD  - Institute of Respiratory Diseases, Xinqiao Hospital of Third Military Medical 
      University, Chongqing 400037, China.
FAU - Wang, Changzheng
AU  - Wang C
AD  - Institute of Respiratory Diseases, Xinqiao Hospital of Third Military Medical 
      University, Chongqing 400037, China.
FAU - Mao, Chengde
AU  - Mao C
AD  - Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
FAU - Zhang, Jianxiang
AU  - Zhang J
AD  - Department of Pharmaceutics, College of Pharmacy, Third Military Medical 
      University, Chongqing 400038, China. Electronic address: jxzhang1980@gmail.com.
FAU - Wang, Guansong
AU  - Wang G
AD  - Institute of Respiratory Diseases, Xinqiao Hospital of Third Military Medical 
      University, Chongqing 400037, China. Electronic address: wanggs2003@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130305
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
RN  - 0 (Cyclodextrins)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (RNA, Messenger)
RN  - 0 (bcl-X Protein)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
SB  - IM
MH  - Acetylation/drug effects
MH  - Apoptosis/drug effects/genetics
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cyclodextrins/*chemistry
MH  - Flow Cytometry
MH  - Gene Expression Regulation/drug effects
MH  - *Gene Transfer Techniques
MH  - Genetic Vectors
MH  - Humans
MH  - Hydrogen-Ion Concentration/drug effects
MH  - Lactic Acid/chemistry
MH  - Microscopy, Confocal
MH  - Nanoparticles/*chemistry/toxicity/ultrastructure
MH  - Oligonucleotides, Antisense/pharmacology
MH  - Polyglycolic Acid/chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - RNA, Messenger/genetics/metabolism
MH  - Transfection
MH  - Viruses/genetics
MH  - bcl-X Protein/genetics/metabolism
EDAT- 2013/03/14 06:00
MHDA- 2013/08/28 06:00
CRDT- 2013/03/14 06:00
PHST- 2013/01/26 00:00 [received]
PHST- 2013/02/11 00:00 [accepted]
PHST- 2013/03/14 06:00 [entrez]
PHST- 2013/03/14 06:00 [pubmed]
PHST- 2013/08/28 06:00 [medline]
AID - S0142-9612(13)00204-4 [pii]
AID - 10.1016/j.biomaterials.2013.02.035 [doi]
PST - ppublish
SO  - Biomaterials. 2013 May;34(16):4159-4172. doi: 10.1016/j.biomaterials.2013.02.035. 
      Epub 2013 Mar 5.