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

IF 2.3 4区医学 Q3 BIOPHYSICS

Cellular and molecular bioengineering Pub Date : 2023-01-17 eCollection Date: 2023-04-01 DOI:10.1007/s12195-022-00757-5

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

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引用次数: 0

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.

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装载 siS100A4 的肿瘤靶向细胞外囊泡用于抑制乳腺癌术后转移

引言S100A4 可促进恶性肿瘤细胞建立肿瘤微环境，而敲除 S100A4 可抑制肿瘤发生。然而，目前还没有针对转移性肿瘤组织中 S100A4 的有效方法。方法：我们设计了 siS100A4-iRGD-EVs 纳米颗粒，并使用 TEM 和 DLS 进行了分析；在体外检测了 siRNA 保护、细胞摄取和 EV 纳米颗粒的细胞毒性。结果：siS100A4-iRGD-EVs 保护 siRNA 免受 RNase 降解，增强了细胞摄取和体外相容性。结果：siS100A4-iRGD-EVs 在体外能保护 siRNA 免受 RNase 的降解，增强了细胞的摄取能力和相容性；在体内，与 siS100A4-EVs 相比，iRGD 修饰的 EVs 能显著增加肿瘤的器官移动性和 siRNA 在肺 PMN 中的积累。结论：siS100A4-iRGD-EVs 纳米颗粒在乳腺癌术后转移小鼠模型中显示出更强的抗转移作用：在线版本包含补充材料，可在10.1007/s12195-022-00757-5上获取。

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来源期刊

Cellular and molecular bioengineering 生物-生物物理

CiteScore

5.60

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.