Purpose

Ultrasound-mediated nanobubbles destruction (UTND) technology could enhance drug transport efficiency and increase the local drug concentration. We structured a novel Olaparib-loaded nanobubbles (Ola-NBs). Then investigated its ability to inhibit triple negative breast cancer (TNBC) cell growth in vitro. Additionally, we observed the change of cisplatin sensitivity before and after Olaparib treatment.

Methods

The Ola-NBs were prepared using extrusion and thin-film hydration combination methods. Cell viability was checked by CCK-8 assay, and calculated the 50% inhibition concentration (IC₅₀) of Olaparib and cisplatin. Next, Jc-1 staining was used to observe mitochondrial membrane depolarization, and an apoptosis assay was applied to assess the apoptosis in different groups. Finally, a Western blot assay was used to evaluate the inhibition effect of Olaparib on TNBC at the molecular level.

Results

Ola-NBs were prepared successfully. The zeta potential was −0.617 ± 0.197 mV, and the average diameter was 473.52 ± 17.33 nm. The IC₅₀ of Olaparib had not significant difference in TNBC cells. However, the IC₉₅ was higher in cisplatin-resistant MDA-MB-231 cells (MDA-MB-231/CDDP). The cell viability decreased following Olaparib treatment and was more obvious in the Ola-NBs group (P < 0.05). In addition, the IC₅₀ of cisplatin was lower in the post-Olaparib treatment group. Jc-1 results revealed that the mitochondrial membrane decreased more strongly in the Ola-NBs and combination therapy groups. And the results of Jc-1 corroborated the apoptosis assay results. Moreover, Bax protein expression level increased, while Bcl-2 protein expression decreased in the treatment groups.

Conclusion

Olaparib not only inhibited TNBC cell growth, but it also improved the sensitivity of cisplatin in TNBC cells. And nanobubbles (NBs) might be an effective supporter, because it can enhance the drug efficacy under ultrasound irradiation.

中文翻译：

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基于纳米颗粒的奥拉帕尼递送增强其效果，并提高三阴性乳腺癌对顺铂的药物敏感性

目的

超声介导的纳米气泡破坏（UTND）技术可以提高药物转运效率并增加局部药物浓度。我们构建了一种新型的装载奥拉帕尼的纳米气泡（Ola-NBs）。然后研究了它在体外抑制三阴性乳腺癌 (TNBC) 细胞生长的能力。此外，我们观察了奥拉帕尼治疗前后顺铂敏感性的变化。

方法

Ola-NBs 是使用挤出和薄膜水合组合方法制备的。通过CCK-8法检测细胞活力，计算奥拉帕尼和顺铂的50％抑制浓度(IC ₅₀ )。接下来，使用Jc-1染色观察线粒体膜去极化，并应用细胞凋亡测定法评估不同组的细胞凋亡。最后，采用蛋白质印迹法在分子水平上评价奥拉帕尼对 TNBC 的抑制作用。

结果

Ola-NBs 制备成功。zeta 电位为 -0.617 ± 0.197 mV，平均直径为 473.52 ± 17.33 nm。Olaparib的IC ₅₀在TNBC细胞中没有显着差异。然而，在顺铂耐药的 MDA-MB-231 细胞 (MDA-MB-231/CDDP) 中，IC _95更高。Olaparib治疗后细胞活力下降，且在Ola-NBs组更为明显（P  < 0.05）。此外，IC ₅₀奥拉帕尼后治疗组的顺铂含量较低。Jc-1 结果显示线粒体膜在 Ola-NB 和联合治疗组中下降得更厉害。Jc-1的结果证实了细胞凋亡检测结果。此外，Bax 蛋白表达水平增加，而 Bcl-2 蛋白表达在治疗组中降低。

结论

奥拉帕尼不仅抑制 TNBC 细胞生长，还提高了顺铂对 TNBC 细胞的敏感性。而纳米气泡（NBs）可能是一种有效的支持物，因为它可以增强超声照射下的药物功效。