Basic research
Galactosylated poly-L-lysine targeted microbubbles for ultrasound mediated antisense c-myc gene transfection in hepatocellular carcinoma cells
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Submission date: 2013-08-01
Final revision date: 2013-09-19
Acceptance date: 2013-09-24
Online publication date: 2015-04-23
Publication date: 2015-04-30
Arch Med Sci 2015;11(2):292–300
Introduction: 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.
Material and 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.