Nanoparticle-based Olaparib delivery enhances its effect, and improves drug sensitivity to cisplatin in triple negative breast cancer

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 (IC 50 ) 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 IC 50 of Olaparib had not significant difference in TNBC cells. However, the IC 95 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 IC 50 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.