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

Authors
  • Pan, Ruiling1
  • He, Tiancheng1
  • Zhang, Kun1
  • Zhu, Lewei1
  • Lin, Jiawei1
  • Chen, Peixian1
  • Liu, Xiangwei1
  • Huang, Huiqi1
  • Zhou, Dan1
  • Li, Wei1
  • Yang, Shuqing1
  • Ye, Guolin1
  • 1 Department of Breast Surgery, The First People's Hospital of Foshan, No. 81 North Lingnan Avenue, Chancheng, Foshan, 528000 Guangdong China. , (China)
Type
Published Article
Journal
Cellular and molecular bioengineering
Publication Date
Apr 01, 2023
Volume
16
Issue
2
Pages
117–125
Identifiers
DOI: 10.1007/s12195-022-00757-5
PMID: 37096069
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. 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. 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. siS100A4-iRGD-EVs nanoparticles show more potent anti-metastasis effect in postoperative breast cancer metastasis mouse model. The online version contains supplementary material available at 10.1007/s12195-022-00757-5. © The Author(s) under exclusive licence to Biomedical Engineering Society 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

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