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Extracellular Microparticles Encapsulated with Diallyl Trisulfide Interfere with the Inflammatory Tumor
Yuping Liu1,2, Rongping Fu1,2, Shumei Tu1,2
1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.
Abstract:
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.
Insights
Diallyl trisulfide microparticles (DATS-MPs) effectively target lung metastasis by interfering with the tumor microenvironment. These DATS-MPs show enhanced antimetastatic effects compared to DATS alone in mouse models.
Area of Science:
- Oncology
- Nanomedicine
- Pharmacology
Background:
- Lung metastasis is a critical factor in the late-stage progression of many solid tumors.
- Diallyl trisulfide (DATS), derived from garlic, exhibits significant antimetastatic properties.
- Limited biocompatible carriers hinder the clinical application of DATS for metastasis treatment.
Purpose of the Study:
- To develop and evaluate extracellular microparticles loaded with DATS (DATS-MPs) for enhanced antimetastatic therapy.
- To investigate the targeting and therapeutic efficacy of DATS-MPs in lung metastasis models.
- To elucidate the mechanism by which DATS-MPs modulate the prometastatic inflammatory microenvironment.
Main Methods:
- Preparation and characterization of DATS-loaded microparticles (DATS-MPs) derived from B16BL6 extracellular vesicles.
- In vitro assessment of DATS-MP interaction with cancer cells and lung epithelial cells.
- In vivo evaluation of DATS-MP biodistribution and antimetastatic efficacy in spontaneous and experimental metastasis mouse models.
- Analysis of molecular markers associated with inflammation and metastasis in lung tissues.
Main Results:
- DATS-MPs were successfully prepared and demonstrated characteristics of extracellular vesicles.
- DATS-MPs showed preferential fusion with cancer cells and lung epithelial cells in vitro.
- Systemically administered DATS-MPs accumulated in lung tissue, the primary site of metastasis.
- DATS-MPs significantly enhanced antimetastatic effects compared to DATS alone in mouse models (p < 0.05).
- DATS-MPs inhibited tumor cell migration and reduced inflammatory markers (S100A8/A9, SAA, IL-6) and key signaling molecules (fibronectin, MRP8, MPO, TLR4-Myd88) in lung tissue.
Conclusions:
- DATS-MPs represent a promising drug delivery system for enhancing the antimetastatic efficacy of DATS.
- DATS-MPs effectively target lung tissue and modulate the prometastatic inflammatory microenvironment.
- The developed DATS-MP system holds potential for improving therapeutic outcomes in metastatic cancer treatment.
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