PMID- 26267649
OWN - NLM
STAT- MEDLINE
DCOM- 20160517
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 8
DP  - 2015
TI  - Ultrasound-targeted microbubble destruction (UTMD) assisted delivery of shRNA 
      against PHD2 into H9C2 cells.
PG  - e0134629
LID - 10.1371/journal.pone.0134629 [doi]
LID - e0134629
AB  - Gene therapy has great potential for human diseases. Development of efficient 
      delivery systems is critical to its clinical translation. Recent studies have 
      shown that microbubbles in combination with ultrasound (US) can be used to 
      facilitate gene delivery. An aim of this study is to investigate whether the 
      combination of US-targeted microbubble destruction (UTMD) and polyethylenimine 
      (PEI) (UTMD/PEI) can mediate even greater gene transfection efficiency than UTMD 
      alone and to optimize ultrasonic irradiation parameters. Another aim of this 
      study is to investigate the biological effects of PHD2-shRNA after its 
      transfection into H9C2 cells. pEGFP-N1 or eukaryotic shPHD2-EGFP plasmid was 
      mixed with albumin-coated microbubbles and PEI to form complexes for 
      transfection. After these were added into H9C2 cells, the cells were exposed to 
      US with various sets of parameters. The cells were then harvested and analyzed 
      for gene expression. UTMD/PEI was shown to be highly efficient in gene 
      transfection. An US intensity of 1.5 W/cm2, a microbubble concentration of 
      300mul/ml, an exposure time of 45s, and a plasmid concentration of 15mug/ml were 
      found to be optimal for transfection. UTMD/PEI-mediated PHD2-shRNA transfection 
      in H9C2 cells significantly down regulated the expression of PHD2 and increased 
      expression of HIF-1alpha and downstream angiogenesis factors VEGF, TGF-beta and bFGF. 
      UTMD/PEI, combined with albumin-coated microbubbles, warrants further 
      investigation for therapeutic gene delivery.
FAU - Zhang, Li
AU  - Zhang L
AD  - Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Hubei Province Key Laboratory of Molecular 
      Imaging, Wuhan, 430022, PR China.
FAU - Sun, Zhenxing
AU  - Sun Z
AD  - Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Hubei Province Key Laboratory of Molecular 
      Imaging, Wuhan, 430022, PR China.
FAU - Ren, Pingping
AU  - Ren P
AD  - Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Hubei Province Key Laboratory of Molecular 
      Imaging, Wuhan, 430022, PR China.
FAU - Lee, Robert J
AU  - Lee RJ
AD  - Division of Pharmaceutics, College of Pharmacy, The Ohio State University, 
      Columbus, Ohio, 43210, United States of America.
FAU - Xiang, Guangya
AU  - Xiang G
AD  - School of Pharmacy, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, 430022, PR China.
FAU - Lv, Qing
AU  - Lv Q
AD  - Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Hubei Province Key Laboratory of Molecular 
      Imaging, Wuhan, 430022, PR China.
FAU - Han, Wei
AU  - Han W
AD  - Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Hubei Province Key Laboratory of Molecular 
      Imaging, Wuhan, 430022, PR China.
FAU - Wang, Jing
AU  - Wang J
AD  - Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Hubei Province Key Laboratory of Molecular 
      Imaging, Wuhan, 430022, PR China.
FAU - Ge, Shuping
AU  - Ge S
AD  - The Heart Center, St. Christopher's Hospital for Children/Drexel University 
      College of Medicine, Philadelphia, Pennsylvania, United States of America.
FAU - Xie, Mingxing
AU  - Xie M
AD  - Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Hubei Province Key Laboratory of Molecular 
      Imaging, Wuhan, 430022, PR China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150812
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Transforming Growth Factor beta)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 9002-98-6 (Polyethyleneimine)
RN  - EC 1.14.11.2 (EGLN1 protein, human)
RN  - EC 1.14.11.29 (Hypoxia-Inducible Factor-Proline Dioxygenases)
SB  - IM
MH  - Cell Line
MH  - Gene Expression/genetics
MH  - *Gene Transfer Techniques
MH  - *Genetic Therapy
MH  - Green Fluorescent Proteins/genetics
MH  - Humans
MH  - Hypoxia-Inducible Factor-Proline Dioxygenases/antagonists & 
      inhibitors/biosynthesis/*genetics
MH  - Microbubbles
MH  - Plasmids/genetics
MH  - Polyethyleneimine/administration & dosage/chemistry
MH  - RNA, Small Interfering/*administration & dosage/genetics
MH  - Transfection
MH  - Transforming Growth Factor beta/genetics
MH  - Ultrasonics
PMC - PMC4534091
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/08/13 06:00
MHDA- 2016/05/18 06:00
PMCR- 2015/08/12
CRDT- 2015/08/13 06:00
PHST- 2015/05/13 00:00 [received]
PHST- 2015/07/11 00:00 [accepted]
PHST- 2015/08/13 06:00 [entrez]
PHST- 2015/08/13 06:00 [pubmed]
PHST- 2016/05/18 06:00 [medline]
PHST- 2015/08/12 00:00 [pmc-release]
AID - PONE-D-15-20775 [pii]
AID - 10.1371/journal.pone.0134629 [doi]
PST - epublish
SO  - PLoS One. 2015 Aug 12;10(8):e0134629. doi: 10.1371/journal.pone.0134629. 
      eCollection 2015.