Tumor-Targeting Extracellular Vesicles Loaded with siS100A4 for Suppressing Postoperative Breast Cancer Metastasis

siS100A4 靶向肿瘤细胞外囊泡抑制乳腺癌术后转移

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作者:Ruiling Pan #, Tiancheng He #, Kun Zhang, Lewei Zhu, Jiawei Lin, Peixian Chen, Xiangwei Liu, Huiqi Huang, Dan Zhou, Wei Li, Shuqing Yang, Guolin Ye

Conclusions

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

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.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12195-022-00757-5.

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