Introduction

S100A4 promotes the establishment of tumor microenvironment for malignant cancer cells, and knockdown of S100A4 can inhibit tumorigenesis. However, there is no efficient way to target S100A4 in metastatic tumor tissues. Here, we investigated the role of siS100A4-loaded iRGD-modified extracellular vesicles (siS100A4-iRGD-EVs) in postoperative breast cancer metastasis.

Methods

siS100A4-iRGD-EVs nanoparticles were engineered and analyzed using TEM and DLS. siRNA protection, cellular uptake, and cytotoxicity of EV nanoparticles were examined in vitro. Postoperative lung metastasis mouse model was created to investigate the tissue distribution and anti-metastasis roles of nanoparticles in vivo.

Results

siS100A4-iRGD-EVs protected siRNA from RNase degradation, enhanced the cellular uptake and compatibility in vitro. Strikingly, iRGD-modified EVs significantly increased tumor organotropism and siRNA accumulation in lung PMNs compared to siS100A4-EVs in vivo. Moreover, siS100A4-iRGD-EVs treatment remarkedly attenuated lung metastases from breast cancer and increased survival rate of mice through suppressing S100A4 expression in lung.

Conclusions

siS100A4-iRGD-EVs nanoparticles show more potent anti-metastasis effect in postoperative breast cancer metastasis mouse model.

中文翻译：

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载有 siS100A4 的肿瘤靶向细胞外囊泡用于抑制术后乳腺癌转移

介绍

S100A4促进恶性癌细胞肿瘤微环境的建立，敲低S100A4可抑制肿瘤发生。然而，目前还没有靶向转移性肿瘤组织中 S100A4 的有效方法。在这里，我们研究了载有 siS100A4 的 iRGD 修饰的细胞外囊泡 (siS100A4-iRGD-EVs) 在乳腺癌术后转移中的作用。

方法

使用 TEM 和 DLS 设计和分析了 siS100A4-iRGD-EVs 纳米粒子。在体外检测了 EV 纳米粒子的 siRNA 保护、细胞摄取和细胞毒性。建立术后肺转移小鼠模型，研究纳米粒子在体内的组织分布和抗转移作用。

结果

siS100A4-iRGD-EVs 保护 siRNA 免受 RNase 降解，增强细胞摄取和体外相容性。引人注目的是，与体内的siS100A4-EV 相比，iRGD 修饰的 EV 显着增加了肺 PMN 中的肿瘤器官性和 siRNA 积累。此外，siS100A4-iRGD-EVs 治疗显着减轻了乳腺癌的肺转移，并通过抑制肺中 S100A4 的表达提高了小鼠的存活率。

结论

siS100A4-iRGD-EVs 纳米粒子在术后乳腺癌转移小鼠模型中显示出更强的抗转移作用。