8-Hydroxyoctanoic acid (8-HOA) produced through cyclooxygenase-2 (COX-2) catalyzed dihomo-γ-linolenic acid (DGLA) peroxidation in delta-5-desaturase inhibitory (D5D siRNA) condition showed an inhibitory effect on breast cancer cell proliferation and migration. However, in vivo use of naked D5D siRNA was limited by off-target silencing and degradation by endonucleases. To overcome the limitation and deliver the D5D siRNA in vivo, we designed an epithelia cell adhesion molecule targeted three-way junctional nanoparticle having D5D siRNA. In this study, we have hypothesized that 3WJ-EpCAM-D5D siRNA will target and inhibit the D5D enzyme in cancer cells leading to peroxidation of supplemented DGLA to 8-HOA resulting in growth inhibitory effect in the orthotopic breast cancer model developed by injecting 4T1 cells. On analysis, we observed a significant reduction in tumor size and metastatic lung nodules in animals treated with a combination of 3WJ-EpCAM-D5D siRNA and DGLA through activating intrinsic apoptotic signaling pathway and by reducing endothelial–mesenchymal damage.

在δ-5-去饱和酶抑制（D5D siRNA）条件下，环氧合酶-2（COX-2）催化二高-γ-亚麻酸（DGLA）过氧化产生的8-羟基辛酸（8-HOA）对乳腺癌细胞显示出抑制作用扩散和迁移。然而，裸露 D5D siRNA 的体内使用受到脱靶沉默和核酸内切酶降解的限制。为了克服限制并在体内递送D5D siRNA，我们设计了一种具有D5D siRNA的上皮细胞粘附分子靶向三路连接纳米颗粒。在这项研究中，我们假设 3WJ-EpCAM-D5D siRNA 将靶向并抑制癌细胞中的 D5D 酶，导致补充的 DGLA 过氧化为 8-HOA，从而在注射 4T1 细胞开发的原位乳腺癌模型中产生生长抑制作用。经过分析，我们观察到，通过激活内在的细胞凋亡信号通路和减少内皮间质损伤，联合使用 3WJ-EpCAM-D5D siRNA 和 DGLA 治疗的动物的肿瘤大小和转移性肺结节显着减小。