Zhao, Gu, Gan, Shao, Chen, Zhu (2020) Exosome-mediated siRNA delivery to suppress postoperative breast cancer metastasis Journal of controlled release : official journal of the Controlled Release Society 318() 1-15


High recurrence and metastasis of triple-negative breast cancer (TNBC) after operation is a leading cause of breast cancer related death. The pre-metastatic niche (PMN) is an environment in a secondary organ conducive to the metastasis of a primary tumor. Herein, we identify exosomes from autologous breast cancer cells that show effective lung targeting ability. Based on this, we developed the biomimetic nanoparticles (cationic bovine serum albumin (CBSA) conjugated siS100A4 and exosome membrane coated nanoparticles, CBSA/siS100A4@Exosome) to improve drug delivery to the lung PMN. CBSA/siS100A4@Exosome self-assembled nanoparticles formed homogeneous sizes of ~200 nm, protected siRNA from degradation, and showed excellent biocompatibility. Further in vivo studies showed that CBSA/siS100A4@Exosome had a higher affinity toward lung in comparison to the CBSA/siS100A4@Liposome, and exhibited outstanding gene-silencing effects that significantly inhibited the growth of malignant breast cancer cells. Taken together, these results indicate that CBSA/siS100A4@Exosome self-assembled nanoparticles are a promising strategy to suppress postoperative breast cancer metastasis. Copyright © 2019 Elsevier B.V. All rights reserved.

手术后三阴性乳腺癌(TNBC)的高复发和转移是乳腺癌相关死亡的主要原因。转移前的生态位(PMN)是辅助器官中有利于原发肿瘤转移的环境。在本文中,我们从自体乳腺癌细胞中鉴定出了具有有效肺靶向能力的外泌体。基于此,我们开发了仿生纳米颗粒(阳离子牛血清白蛋白(CBSA)缀合的siS100A4和外泌体膜包被的纳米颗粒CBSA / siS100A4 @ Exosome),以改善药物向肺PMN的递送。 CBSA / siS100A4 @ Exosome自组装纳米颗粒形成约200 nm的均一尺寸,保护siRNA免受降解,并显示出优异的生物相容性。进一步的体内研究表明,与CBSA / siS100A4 @脂质体相比,CBSA / siS100A4 @ Exosome对肺具有更高的亲和力,并且表现出显着的基因沉默效应,该效应显着抑制了恶性乳腺癌细胞的生长。综上所述,这些结果表明,CBSA / siS100A4 @ Exosome自组装纳米颗粒是抑制术后乳腺癌转移的一种有前途的策略。版权所有©2019.由Elsevier BV发布



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