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

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 ext...

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Published in:Cellular and molecular bioengineering 2023-04, Vol.16 (2), p.117-125
Main Authors: Pan, Ruiling, He, Tiancheng, Zhang, Kun, Zhu, Lewei, Lin, Jiawei, Chen, Peixian, Liu, Xiangwei, Huang, Huiqi, Zhou, Dan, Li, Wei, Yang, Shuqing, Ye, Guolin
Format: Article
Language:English
Subjects:
Biocompatibility
Biological and Medical Physics
Biomaterials
Biomedical Engineering and Bioengineering
Biomedical Engineering/Biotechnology
Biophysics
Breast cancer
Cell Biology
Cytotoxicity
Engineering
Extracellular vesicles
In vivo methods and tests
Lung cancer
Lungs
Metastases
Metastasis
Nanoparticles
Organotropism
Original
Original Article
Ribonuclease
S100A4 protein
siRNA
Survival
Toxicity
Tumor microenvironment
Tumorigenesis
Tumors
Vesicles
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Summary: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.
ISSN:1865-5025
1865-5033
DOI:10.1007/s12195-022-00757-5