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

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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.

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Funding

This study was supported by Science and technology innovation project of Foshan (2220001003854, 2220001004847), Medical research project of Foshan Health Bureau (20220479), GuangDong Basic and Applied Basic Research Foundation (2021A1515111087), Medical Scientific Research Foundation of Guangdong Province (A2022509).

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Author notes

  1. Ruiling Pan and Tiancheng He contributed equally to this work.

Authors and Affiliations

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

    Ruiling Pan, Tiancheng He, Kun Zhang, Lewei Zhu, Jiawei Lin, Peixian Chen, **angwei Liu, Huiqi Huang, Dan Zhou, Wei Li, Shuqing Yang & Guolin Ye

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  1. Ruiling Pan
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Correspondence to Guolin Ye.

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All animal studies were carried out following the protocols established by the Ethics Committee of the First People’s Hospital of Foshan.

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Pan, R., He, T., Zhang, K. et al. Tumor-Targeting Extracellular Vesicles Loaded with siS100A4 for Suppressing Postoperative Breast Cancer Metastasis. Cel. Mol. Bioeng. 16, 117–125 (2023). https://doi.org/10.1007/s12195-022-00757-5

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