title: Galactosylated poly-L-lysine targeted microbubbles for ultrasound mediated antisense c-myc gene transfection in hepatocellular carcinoma cells.
abstract: BACKGROUND
  The aim of the study was to investigate the efficiency of delivery and targeted binding of c-myc antisense oligodeoxynucleotide (ASODN) and find a novel therapy for hepatic carcinoma.
  
  
  METHODS
  A targeted ultrasound microbubble compound was synthesized to deliver the c-myc ASODN by ultrasound-targeted microbubble destruction (UTMD) and applied in hepatocellular carcinoma cells (HCC) and cancer bearing mice. Lipid microbubbles were conjugated with biotinylated galactosylated poly-L-lysine (G-PLL) and SonoVue to target the hepatocellular carcinoma SMMC7721 cells with asialoglycoprotein receptors. There were four groups in both in vitro and in vivo studies: control group (group A); c-myc ASODN + G-PLL (CG group, group B); c-myc ASODN + SonoVue (CUS group, group C); c-myc ASODN + G-PLL + SonoVue (CGUS group, group D). The expression of c-myc mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR), and proliferation investigations of the SMMC7721 cells were also performed. In addition, the tumor volume was calculated and compared among different groups.
  
  
  RESULTS
  The level of c-myc mRNA in the three experimental groups was significantly lower than that in the control group in vitro (p < 0.05). Furthermore, c-myc gene expression was suppressed more strongly in the CGUS group compared with other groups in both in vitro and in vivo studies (p < 0.05). In addition, ultrasound mediation of targeted microbubbles yielded the highest inhibition of tumor growth and cell proliferation among the four groups.
  
  
  CONCLUSIONS
  The use of a G-PLL targeted microbubble contrast agent combined with ultrasound exposure could be a potential method for increasing gene delivery efficiency. This technique is a promising nonviral approach that can be used in liver cancer.
authors.affiliation: Department of Ultrasound, Harbin Medical Univeristy Cancer Hospital, Harbin, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jing
authors.affiliation: Department of Ultrasound, Harbin Medical Univeristy Cancer Hospital, Harbin, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Department of Ultrasound, Harbin Medical Univeristy Cancer Hospital, Harbin, China.
authors.forename: Jiu-Wei
authors.initials: JW
authors.lastname: Zhang
authors.affiliation: Department of Ultrasound, Harbin Medical Univeristy Cancer Hospital, Harbin, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Ultrasound, Harbin Medical Univeristy Cancer Hospital, Harbin, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Shao
authors.affiliation: Department of Ultrasound, Harbin Medical Univeristy Cancer Hospital, Harbin, China.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Sun
keywords: C-myc; antisense oligodeoxynucleotide; galactosylated poly-L-lysine; hepatocellular carcinoma cell; microbubble