However, previous studies of therapeutic gene delivery using UTMD have paid more attention to increasing the penetration of the cell membrane via physical bioeffects [10, 11], and few studies have been carried out to target gene breakthrough in the nuclear barrier during UTMD transfection in an effective manner.
For the mechanism of UTMD, microbubbles may serve as cavitation nuclei to accomplish sonoporation during ultrasound irradiation which creates transient and reversible pores on the cell membrane.
Based these factors, this study aimed to develop a novel gene transfection system composed of UTMD and NLS and to investigate the therapeutic potential of this system for treating ischemic heart disease by transfecting the Ang-1 gene into a canine myocardial infarction model.
UTMD was performed using a Vivid Q ultrasound diagnostic platform (GE Healthcare, WI, USA) equipped with a M5S transducer (1.7-3.3 MHz).
To determine the safety of the gene delivery system composed of UTMD and NLS, the level of myocardial enzyme cardiac Troponin I (cTnI) before and after transfection of each group was detected.
The relative expression of Ang-1 protein in group C was 1.6-fold higher than group B, which indicated that UTMD combined with NLS could effectively promote gene expression than UTMD alone (Figure 4).
These results indicated that UTMD combined with NLS-mediated Ang-1 gene delivery contributed to the attenuation of the myocardial fibrosis and MI area.
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