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首页> 外文期刊>The Journal of Steroid Biochemistry and Molecular Biology >Microbubble-enhanced ultrasound to deliver an antisense oligodeoxynucleotide targeting the human androgen receptor into prostate tumours.
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Microbubble-enhanced ultrasound to deliver an antisense oligodeoxynucleotide targeting the human androgen receptor into prostate tumours.

机译：微气泡增强型超声将靶向人雄激素受体的反义寡聚脱氧核苷酸传递到前列腺肿瘤中。

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摘要

We have shown recently that downregulation of the androgen receptor (AR), one of the key players in prostate tumor cells, with short antisense oligodeoxynucleotides (ODNs) results in inhibition of prostate tumor growth. Particularly with regard to an application of these antisense drugs in vivo, we now investigated the usefulness of microbubble-enhanced ultrasound to deliver these ODNs into prostate cancer cells. Our short antisense AR ODNs were loaded onto the lipid surface of cationic gas-filled microbubbles by ion charge binding, and delivered into the cells by bursting the loaded microbubbles with ultrasound. In vitro experiments were initially performed to show that this kind of delivery system works in principle. In fact, transfection of prostate tumor cells with antisense AR ODNs using microbubble-enhanced ultrasound resulted in 49% transfected cells, associated with a decrease in AR expression compared to untreated controls. In vivo, uptake of a digoxigenin-labelled ODN was found in prostate tumour xenografts in nude mice following intratumoral or intravenous injection of loaded microbubbles and subsequent exposure of the tumour to ultrasound, respectively. Our results show that ultrasound seems to be the driving force of this delivery system. Uptake of the ODN was also observed in tumors after treatment with ultrasound alone, with only minor differences compared to the combined use of microbubbles and ultrasound.
机译：我们最近发现，用短的反义寡聚脱氧核苷酸（ODN）对雄激素受体（AR）的下调是前列腺肿瘤细胞的关键因素之一，从而抑制了前列腺肿瘤的生长。特别是关于这些反义药物在体内的应用，我们现在研究了微泡增强超声将这些ODN传递到前列腺癌细胞中的有用性。通过离子电荷结合将我们的短反义AR ODNs负载到阳离子充气微气泡的脂质表面上，并通过用超声波使负载的微气泡破裂而将其递送到细胞中。最初进行了体外实验，以表明这种输送系统原则上可以工作。实际上，使用微气泡增强型超声用反义AR ODN转染前列腺肿瘤细胞可导致49％的细胞被转染，与未处理的对照组相比，AR表达下降。在体内，在肿瘤内或静脉内注射负载的微泡并随后将肿瘤暴露于超声之后，在裸鼠的前列腺肿瘤异种移植物中发现了洋地黄毒苷标记的ODN的摄取。我们的结果表明，超声似乎是这种输送系统的驱动力。单独使用超声治疗后，在肿瘤中也观察到了ODN的吸收，与微泡和超声的联合使用相比仅有很小的差异。

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