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Development of double strand RNA mPEI nanoparticles and application in treating invasive breast cancer

机译：双链RNA mPEI纳米颗粒的开发及其在浸润性乳腺癌中的应用

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Triple negative breast cancer (TNBC) has been characterized as a very heterogeneous subtype, and is more invasive and non-expressing of the genes for the estrogen receptor (ER), progesterone receptor (PR) and HER2eu, with poor prognosis, and hence the efficacy of regular chemotherapy is very limited. Here, we report a kind of double strand RNA (dsRNA) mPEI nanoparticle for treatment of invasive TNBC. The studies were performed on TNBC cells in vitro and in TNBC cancer-bearing mice. The results showed that dsRNA mPEI nanoparticles were able to effectively transfect cells, and demonstrated a strong capability in knocking-down the Fra-1 gene and down-stream MMP-1 and MMP-9 genes in TNBC cells and TNBC cancer-bearing mice, thereby inhibiting the invasion and migration of cells. After intratumoral injection, dsRNA mPEI nanoparticles exhibited a robust anticancer efficacy in TNBC cancer-bearing mice, and the anticancer efficacy was superior to that of paclitaxel. In conclusion, dsRNA mPEI nanoparticles are able to effectively treat aggressive TNBC, and the mechanism studies reveal that they take effect by knocking-down Fra-1 relevant genes, hence interfering in transcription and translation of the genes, which are necessary for growth and metastasis of TNBC. Therefore, the present study offers a new and promising formulation and strategy for effective treatment of TNBC.
机译：三阴性乳腺癌（TNBC）具有非常异质的亚型特征，其雌激素受体（ER），孕激素受体（PR）和HER2 / neu的基因更具侵袭性且不表达，预后较差，并且因此常规化疗的疗效非常有限。在这里，我们报告一种双链RNA（dsRNA）mPEI纳米粒子治疗侵袭性TNBC。这项研究是在TNBC细胞和TNBC荷瘤小鼠中进行的。结果表明，dsRNA mPEI纳米颗粒能够有效转染细胞，并显示出强大的敲除TNBC细胞和TNBC荷瘤小鼠中Fra-1基因以及下游MMP-1和MMP-9基因的能力，从而抑制细胞的侵袭和迁移。肿瘤内注射后，dsRNA mPEI纳米颗粒在TNBC荷瘤小鼠中显示出强大的抗癌功效，并且抗癌功效优于紫杉醇。总之，dsRNA mPEI纳米颗粒能够有效治疗侵袭性TNBC，其机理研究表明，它们可通过敲低Fra-1相关基因来发挥作用，从而干扰了基因的转录和翻译，这对于生长和转移至关重要TNBC。因此，本研究为有效治疗TNBC提供了一种新的有希望的配方和策略。

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