来自美国的华人科学家Zheng-Rong Lu在国际学术期刊cancer research发表了一篇文章，他们针对β3整合素设计了siRNA并通过纳米颗粒进行体内转运能够显著抑制三阴性乳腺癌的生长，转移和复发，具有重要 应用前景。
转移性乳腺癌是癌症导致女性死亡的第二大杀手，而三阴性乳腺癌是乳腺癌中具有高度侵袭性的一个亚型，到目前为止，仍缺少了解比较清楚的分子靶向目标以制定有效的靶向治疗策略。疾病复发，转移以及对药物的抵抗导致正常的化疗手段对于三阴性乳腺癌治疗不能达到有效的治疗效果。
之前有研究表明β3整合素与上皮细胞间充质转化和癌症转移具有紧密联系，因此研究人员提出利用纳米颗粒携带针对β3整合素设计的siRNA，以β3整合素为靶向目标进行三阴性乳腺癌治疗。
研究人员利用携带siRNA的纳米颗粒处理三阴性乳腺癌细胞，能够有效抑制β3整合素的表达，减弱TGFb介导的上皮细胞间充质转化和侵袭，重 建TGFb介导的对癌细胞生长的抑制，并抑制3D类器官生长。研究人员又对该纳米颗粒进行了改造，增强了已发生EMT过程的细胞对siRNA的摄取能力。 随后，研究人员利用静脉注射的方法将改造后携带siRNA的纳米颗粒注入小鼠静脉，结果发现小鼠原位肿瘤负荷减小，并且显著抑制了癌细胞的转移。除此之 外，他们还对携带TGFb预处理的MDA-MB-231肿瘤的小鼠进行了该药物处理，肿瘤的转移，原位肿瘤切除后的癌症复发都受到显著抑制。
总的来说，这项研究表明利用纳米颗粒携带靶向β3整合素的siRNA治疗三阴性乳腺癌具有重要应用前景。
doi: 10.1158/0008-5472.CAN-14-3485
Silencing β3 Integrin by Targeted ECO/siRNA Nanoparticles Inhibits EMT and Metastasis of Triple Negative Breast Cancer
Jenny G Parvani1, Maneesh D. Gujrati1, Margaret A. Mack1, William P. Schiemann2, and Zheng-Rong Lu
Metastatic breast cancer is the second leading cause of cancer-related deaths amongst women. Triple-negative breast cancer (TNBC) is a highly aggressive subcategory of breast cancer and currently lacks well-defined molecular targets for effective targeted therapies. Disease relapse, metastasis, and drug resistance render standard chemotherapy ineffective in the treatment of TNBC.Since previous studies coupled β3 integrin to epithelial-mesenchymal transition (EMT) and metastasis, we exploited β3 integrin as a therapeutic target to treat TNBC by delivering β3 integrin siRNA via lipid ECO-based nanoparticles (ECO/siβ3). Treatment of TNBC cells with ECO/siβ3 was sufficient to effectively silence β3 integrin expression, attenuate TGF-β-mediated EMT and invasion, restore TGF-β-mediated cytostasis, and inhibit 3-dimensional organoid growth. Modification of ECO/siβ3 nanoparticles with an RGD peptide via a PEG spacer enhanced siRNA uptake by post-EMT cells. Intravenous injections of RGD-targeted ECO/siβ3 nanoparticles in vivo alleviated primary tumor burden, and more importantly, significantly inhibited metastasis. Mice bearing orthotopic, TGF-β-pre-stimulated MDA-MB-231 tumors that were treated with RGD-targeted ECO/siβ3 nanoparticles were free of metastases and relapse after primary tumor resection and 4 weeks after release from the treatment, in comparison to untreated mice. Collectively, these results highlight ECO/siβ3 nanoparticles as a promising therapeutic regimen to combat TNBC.
