当前位置: X-MOL 学术Pharm. Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Enhanced Cellular Uptake and Gene Silencing Activity of Survivin-siRNA via Ultrasound-Mediated Nanobubbles in Lung Cancer Cells.
Pharmaceutical Research ( IF 3.7 ) Pub Date : 2020-08-05 , DOI: 10.1007/s11095-020-02885-x
Hasan Akbaba 1 , Gülşah Erel-Akbaba 1, 2 , Mustafa Kotmakçı 1 , Yücel Başpınar 1
Affiliation  

Purpose

Paclitaxel is a first-line drug for the therapy of lung cancer, however, drug resistance is a serious limiting factor, related to overexpression of anti-apoptotic proteins like survivin. To overcome this phenomenon, developing novel ultrasound responsive nanobubbles - nanosized drug delivery system- for the delivery of paclitaxel and siRNA in order to silence survivin expression in the presence of ultrasound was aimed.

Methods

Paclitaxel-carrying nanobubble formulation was obtained by modifying the multistep method. Then, the complex formation of the nanobubbles - paclitaxel formulation with survivin-siRNA, was examined in terms of particle size, polydispersity index, zeta potential, and morphology. Furthermore, siRNA binding and protecting ability, cytotoxicity, cellular uptake, gene silencing, and induction of apoptosis studies were investigated in terms of lung cancer cells.

Results

Developed nanobubbles have particle sizes of 218.9–369.6 nm, zeta potentials of 27–34 mV, were able to protect siRNA from degradation and delivered siRNA into the lung cancer cells. Survivin expression was significantly lower compared with the control groups and enhanced apoptosis was induced by the co-delivery of survivin-siRNA and paclitaxel. Furthermore, significantly higher effects were obtained in the presence of ultrasound induction.

Conclusion

The ultrasound responsive nanobubble system carrying paclitaxel and survivin-siRNA is a promising and effective approach against lung cancer cells.


中文翻译:

超声介导的纳米气泡在肺癌细胞中增强了Survivin-siRNA的细胞摄取和基因沉默活性。

目的

紫杉醇是用于治疗肺癌的一线药物,但是,耐药性是一个严重的限制因素,与抗凋亡蛋白(如生存蛋白)的过度表达有关。为了克服这一现象,目标是开发新型的超声波响应纳米气泡-纳米级药物输送系统-用于输送紫杉醇和siRNA,从而在存在超声的情况下使survivin表达沉默。

方法

通过修改多步法获得了载有紫杉醇的纳米气泡制剂。然后,根据粒径,多分散指数,ζ电势和形态检查了纳米气泡-紫杉醇制剂与survivin-siRNA的复合物形成。此外,针对肺癌细胞,研究了siRNA的结合和保护能力,细胞毒性,细胞摄取,基因沉默和凋亡诱导研究。

结果

发达的纳米气泡的粒径为218.9–369.6 nm,ζ电位为27–34 mV,能够保护siRNA免受降解,并将siRNA输送到肺癌细胞中。与对照组相比,survivin表达明显降低,并且通过survivin-siRNA和紫杉醇的共同递送诱导凋亡增强。此外,在超声感应的存在下获得了明显更高的效果。

结论

携带紫杉醇和survivin-siRNA的超声响应纳米气泡系统是一种有前途和有效的抗肺癌细胞的方法。
更新日期:2020-08-05
down
wechat
bug