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

机译：双链RNA MPEI纳米粒子的研制及其在治疗侵袭性乳腺癌中的应用

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摘要

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 HER2/neu, 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）已被表征为非常异质亚型，并且是更侵入性和非表达的基因对雌激素受体（ER），孕酮受体（PR）和HER2 / neu的，具有不良预后，和因此定期化疗的疗效是非常有限的。在这里，我们报告了一种双链RNA（dsRNA的）mPEI纳米颗粒的治疗三阴性乳腺癌侵袭性的。该研究是在TNBC细胞在体外和TNBC罹癌小鼠中进行。结果表明，dsRNA的mPEI纳米颗粒能够有效转染的细胞，并在表现出强有力的能力击倒在FRA-1基因和下游MMP-1和MMP-9基因在TNBC细胞和TNBC患癌小鼠，从而抑制细胞的侵袭和迁移。瘤内注射后，dsRNA的mPEI纳米颗粒表现出TNBC患癌小鼠鲁棒抗癌功效，和抗癌功效优于紫杉醇。总之，双链RNA mPEI纳米颗粒能够有效地治疗侵略性三阴，其作用机制研究表明，它们生效通过击倒FRA-1相关的基因，因而在基因，这是必要的生长和转移的转录和翻译的干扰TNBC的。因此，本研究提供了有效的治疗三阴性乳腺癌的新的有前途的制定和战略。

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  • 来源
    《RSC Advances》 |2019年第23期|共15页
  • 作者

    Liu Rui; Mu Li-Min; Bai Jing; Du Ya-Fei; Xie Ying; Lu Wan-Liang;

  • 作者单位

    Peking Univ Sch Pharmaceut Sci State Key Lab Nat &

    Biomimet Drugs Beijing Key Lab Mol Pharmaceut &

    New Drug Syst Beijing 100191 Peoples R China;

    Peking Univ Sch Pharmaceut Sci State Key Lab Nat &

    Biomimet Drugs Beijing Key Lab Mol Pharmaceut &

    New Drug Syst Beijing 100191 Peoples R China;

    Peking Univ Sch Pharmaceut Sci State Key Lab Nat &

    Biomimet Drugs Beijing Key Lab Mol Pharmaceut &

    New Drug Syst Beijing 100191 Peoples R China;

    Peking Univ Sch Pharmaceut Sci State Key Lab Nat &

    Biomimet Drugs Beijing Key Lab Mol Pharmaceut &

    New Drug Syst Beijing 100191 Peoples R China;

    Peking Univ Sch Pharmaceut Sci State Key Lab Nat &

    Biomimet Drugs Beijing Key Lab Mol Pharmaceut &

    New Drug Syst Beijing 100191 Peoples R China;

    Peking Univ Sch Pharmaceut Sci State Key Lab Nat &

    Biomimet Drugs Beijing Key Lab Mol Pharmaceut &

    New Drug Syst Beijing 100191 Peoples R China;

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