Extracellular Microparticles Encapsulated with Diallyl Trisulfide Interfere with the Inflammatory Tumor Microenvironment and Lung Metastasis of Invasive Melanoma
| Autor: | Li Tao, Shumei Tu, Chengyao Ma, Rongping Fu, Ding Qu, Yuping Liu, Congyan Liu, Yan Chen, Yang Zhao, Xiaoqi Li |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Lung Neoplasms
Pharmaceutical Science 02 engineering and technology Sulfides 030226 pharmacology & pharmacy Extracellular Vesicles Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Movement Cell Line Tumor mental disorders Drug Discovery Tumor Microenvironment Extracellular medicine Animals Calgranulin A Serum amyloid A Lung Melanoma Peroxidase Inflammation Tumor microenvironment biology Interleukin-6 Chemistry Epithelial Cells 021001 nanoscience & nanotechnology medicine.disease Fibronectins Allyl Compounds Toll-Like Receptor 4 Fibronectin Diallyl trisulfide Myeloperoxidase Cancer cell Cancer research biology.protein Molecular Medicine 0210 nano-technology |
| Zdroj: | Molecular Pharmaceutics. 18:822-835 |
| ISSN: | 1543-8392 1543-8384 |
| DOI: | 10.1021/acs.molpharmaceut.0c00696 |
| Popis: | Lung metastasis is a fatal and late-stage event for many solid tumors. Multiple lines of evidence have demonstrated that diallyl trisulfide (DATS), an active ingredient of garlic, possesses striking antimetastatic effects. However, the lack of highly efficient organ-compatible carriers restricts its application. In the present study, we showed that extracellular microparticles encapsulated with DATS (DATS-MPs) were capable of interfering with the prometastatic inflammatory microenvironment in local tissues. DATS-MPs were successfully prepared and exhibited typical characteristics of B16BL6-derived extracellular vesicles. The DATS-MPs preferentially fused with cancer cells and endogenous cells (mouse lung epithelial MLE-12 cells) from the metastatic organs in vitro. More interestingly, the systemically administered MPs predominantly accumulated in the lung tissue that serves as their main metastatic organ. The drug-loaded MPs exerted higher antimetastatic effects than DATS alone in both the spontaneous and the experimental metastasis models in mice (*p < 0.05). Additionally, we found that DATS-MPs inhibited tumor cell migration and interfered with the prometastatic inflammatory microenvironment via decreasing the release of S100A8/A9, serum amyloid A (SAA), and interleukin-6 (IL-6) and inhibiting the expression of fibronectin, MRP8, myeloperoxidase (MPO), and the toll-like receptor 4 (TLR4)-Myd88 in the lung tissues. Collectively, DATS-MPs appeared to enhance the antimetastatic efficiency of DATS in animal models under study. |
| Databáze: | OpenAIRE |
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