Ultrasound-sensitive siRNA-loaded nanobubbles fabrication and antagonism in drug resistance for NSCLC.

Ultrasound-sensitive siRNA-loaded nanobubbles fabrication and antagonism in drug resistance for NSCLC.
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超声敏感的 siRNA 纳米气泡的制备及其对 NSCLC 耐药性的拮抗作用

DOI:
10.1080/10717544.2021.2021321
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发表时间:
2022-12
期刊:
影响因子:
6
通讯作者:
Nie F
Nie F
中科院分区:
医学2区
文献类型:
--
作者:
Su C;Ren X;Yang F;Li B;Wu H;Li H;Nie F

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摘要由于缺乏安全、有效的基因靶向递送技术。在本研究中,我们制备了载PDLIM 5 siRNA的纳米气泡(PDLIM 5siRNA-NBs),以研究其转染效率及其与超声照射联合治疗非小细胞肺癌(NSCLC)的耐药性拮抗作用。研究结果表明,PDLIM 5 siRNA能有效地结合在平均粒径为191.6 ± 0.50 nm、Zeta电位为11.8 ± 0.68 mV的纳米棒外壳上。超声成像表明PDLIM 5 siRNA NB保持与微泡(SonoVue)相同的信号。在0.5W/m2超声强度和1 min照射时间的优化条件下,PC 9 GR细胞的转染效率最高为90.23 ± 1.45%,PDLIM 5 mRNA和蛋白表达均受到抑制。更重要的是,在超声照射的帮助下,制造的PDLIM 5siRNA-NB的抗肿瘤作用已被证明显著抑制肿瘤细胞生长并促进凋亡。因此,携带PDLIM 5siRNA的NB有可能作为基因载体结合超声照射对抗NSCLC的耐药性。
Abstract Due to the lack of safe, effective, and gene-targeted delivery technology. In this study, we have prepared nanobubbles loaded PDLIM5 siRNA (PDLIM5siRNA-NBs) to investigate the transfection efficiency and their antagonism in drug resistance in combination with ultrasound irradiation for non-small-cell lung cancer (NSCLC). Research results show that the PDLIM5 siRNA are effectively bound to the shell of NBs with a mean diameter of 191.6 ± 0.50 nm and a Zeta potential of 11.8 ± 0.68 mV. And the ultrasonic imaging indicated that the PDLIM5 siRNA NBs maintain the same signals as the microbubbles (SonoVue). Under the optimized conditions of 0.5 W/m2 ultrasound intensity and 1 min irradiation duration, the highest transfection efficiency of PC9GR cells was 90.23 ± 1.45%, which resulted in the inhibition of PDLIM5 mRNA and protein expression. More importantly, the anti-tumor effect of fabricated PDLIM5siRNA-NBs with the help of ultrasound irradiation has been demonstrated to significantly inhibit tumor cell growth and promote apoptosis. Therefore, NBs carrying PDLIM5siRNA may have the potential to act as gene vectors combined with ultrasound irradiation to antagonize drug resistance for NSCLC.
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