Ultrasound Selleck Tipifarnib microbubbles mostly contain gas [9]. The composition of its shell may include albumin, lipids, saccharide, non-ionic surfactants, polymers and other materials [10]. At present the size has been developed to nano-scale and it has the ability to penetrate the vascular endothelium [11]. Microbubbles containing gas will be compressed and expansed under the action of ultrasound with a certain intensity and frequency. When the sound energy reaches certain intensity, the microbubbles are immediately crushed. This will

produce cavitation effect and mechanical effect to increase the permeability of cell membrane structure in target region, make the microvessels with the diameter ≤7 μm break down, widen the intercellular gap of vascular endothelial cells. The exogenous genes can easily penetrate into the tissues and cells through capillary vessels to improve the gene transfection rate and expression [12, 13]. Cavitation effect can also damage cells,

inhibit cell proliferation, and promote tumor cell apoptosis. When ultrasound-targeted microbubble generates strong cavitation effects, it can also damage blood vessel wall, active endogenous or exogenous coagulation, induce large-scale capillary embolism and block nutrient supply to cancerous cells, leading to disappearance of tumor tissues [14, 15]. Suicide gene therapy has been

widely used in liver cancer treatment and showed a good application prospect. Especially Fer-1 nmr the herpes simplex virus thymus kinase/TPCA-1 mw ganciclovir (HSV-TK/GCV) therapy system is most widely applied. HSV-TK is a prodrug enzyme gene which can express and produce TK in the tumor cells, catalyze nucleoside analogue to form mono- phosphate products, and further form a triphosphoric Edoxaban acid product under the effect of phosphokinase in the cell. As a chain terminator, it will interfere with DNA synthesis during cell division, leading to tumor cell death [16, 17]. A large number of studies have shown that suicide gene system also has a “”bystander effect”". The effect will kill non-transfected cells with the transfected cells, which overcomes the shortcomings of the low gene transtection rate and greatly enhances the anti-tumor effect of suicide gene therapy [18]. In this study, ultrasound microbubbles wrapped HSV-TK suicide gene had targeted release in mice liver tissues, and improved gene transfection efficiency with the features of ultrasound and microbubbles. In addition, the bystander effect of suicide gene fully played the anti-tumor role. The study provided an efficient, relatively targeted, non-invasive, and physical gene transfection method for HSV-TK/GCV system.

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