负载siS100A4的肿瘤靶向细胞外囊泡用于抑制乳腺癌术后转移
Tumor-Targeting Extracellular Vesicles Loaded with siS100A4 for Suppressing Postoperative Breast Cancer Metastasis.
作者信息
Pan Ruiling, He Tiancheng, Zhang Kun, Zhu Lewei, Lin Jiawei, Chen Peixian, Liu Xiangwei, Huang Huiqi, Zhou Dan, Li Wei, Yang Shuqing, Ye Guolin
机构信息
Department of Breast Surgery, The First People's Hospital of Foshan, No. 81 North Lingnan Avenue, Chancheng, Foshan, 528000 Guangdong China.
出版信息
Cell Mol Bioeng. 2023 Jan 17;16(2):117-125. doi: 10.1007/s12195-022-00757-5. eCollection 2023 Apr.
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 . Postoperative lung metastasis mouse model was created to investigate the tissue distribution and anti-metastasis roles of nanoparticles .
RESULTS
siS100A4-iRGD-EVs protected siRNA from RNase degradation, enhanced the cellular uptake and compatibility . Strikingly, iRGD-modified EVs significantly increased tumor organotropism and siRNA accumulation in lung PMNs compared to siS100A4-EVs . 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.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s12195-022-00757-5.
引言
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，在转移性肿瘤组织中尚无有效的靶向S100A4的方法。在此，我们研究了负载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
构建siS100A4-iRGD-EVs纳米颗粒并使用透射电子显微镜（TEM）和动态光散射（DLS）进行分析。检测EV纳米颗粒的siRNA保护、细胞摄取及细胞毒性。建立术后肺转移小鼠模型以研究纳米颗粒的组织分布及抗转移作用。
结果
siS100A4-iRGD-EVs可保护siRNA不被核糖核酸酶降解，增强细胞摄取及相容性。引人注目的是，与siS100A4-EVs相比，iRGD修饰的EVs显著增加了肿瘤向肺的器官趋向性及siRNA在肺多形核中性粒细胞（PMN）中的蓄积。此外，siS100A4-iRGD-EVs治疗通过抑制肺中S100A4的表达，显著减轻了乳腺癌的肺转移并提高了小鼠的生存率。
结论
siS100A4-iRGD-EVs纳米颗粒在乳腺癌术后转移小鼠模型中显示出更强的抗转移作用。
补充信息
网络版包含可在10.1007/s12195-022-00757-5获取的补充材料。
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