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

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

doi:10.1007/s12195-022-00757-5

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

Cell Mol Bioeng. 2023 Jan 17;16(2):117-125. doi: 10.1007/s12195-022-00757-5. eCollection 2023 Apr.

Authors

Ruiling Pan^#¹, Tiancheng He^#¹, Kun Zhang¹, Lewei Zhu¹, Jiawei Lin¹, Peixian Chen¹, Xiangwei Liu¹, Huiqi Huang¹, Dan Zhou¹, Wei Li¹, Shuqing Yang¹, Guolin Ye¹

Affiliation

¹ Department of Breast Surgery, The First People's Hospital of Foshan, No. 81 North Lingnan Avenue, Chancheng, Foshan, 528000 Guangdong China.

^# Contributed equally.

Abstract

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.

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

Keywords: Postoperative breast cancer metastasis; S100A4; Tumor-targeting; iRGD-modified EVs.

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