Tumor-Targeting Extracellular Vesicles Loaded with SiS100A4 for Suppressing Postoperative Breast Cancer Metastasis

Overview

Journal Cell Mol Bioeng

Publisher Springer

Specialty Biomedical Engineering

Date 2023 Apr 25

PMID 37096069

Authors

Ruiling Pan

Tiancheng He

Kun Zhang

Lewei Zhu

Jiawei Lin

Peixian Chen

Xiangwei Liu

Huiqi Huang

Dan Zhou

Wei Li

Shuqing Yang

Guolin Ye

Affiliations

Soon will be listed here.

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 . 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.

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