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Published on: May 22, 2020
Magnetic nanoparticle carrying verbascoside suppresses oral squamous cell carcinoma progression by targeting ICAM1
Mifang Yang1, Jingjing Wu2, Yuan Jing3
1Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, PR China.
Abstract:
Oral squamous cell carcinoma (OSCC), the most common oral malignancy, requires innovative therapeutic strategies. We developed a magnetic nanoparticle carrying verbascoside (VB-Fe3O4) to enhance the bioavailability and antitumor efficacy of VB, a bioactive compound from Rehmannia glutinosa. VB-Fe3O4 demonstrated superior tumor-targeting capabilities, achieving higher drug accumulation compared with free VB. In the human OSCC cell line HSC-3, VB-Fe3O4 markedly induced apoptosis, inhibited proliferation and invasion through IL-6/STAT3 pathway. Mechanistic studies screened out intercellular cell adhesion molecule 1 (ICAM1) as the primary target of VB, with VB-Fe3O4 suppressing IL-6-induced STAT3 phosphorylation. VB-Fe3O4 downregulated metastasis-related genes, such as vascular cell adhesion molecule 1, mucin 1, ezrin, and invasion factor matrix metalloproteinase-9, were markedly decreased by VB-Fe3O4. VB-Fe3O4 showed greater tumor suppression in OSCC transplanted tumors and experimental metastasis tumors compared with free VB. This nanoplatform synergistically combines precision delivery and molecular targeting, offering a promising treatment for OSCC management.
Insights
Magnetic nanoparticles carrying verbascoside (VB-Fe3O4) effectively target oral squamous cell carcinoma (OSCC). This novel nanoplatform enhances antitumor efficacy by inhibiting cancer cell growth, invasion, and metastasis.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Oral squamous cell carcinoma (OSCC) is a prevalent malignancy demanding novel therapeutic approaches.
- Verbascoside (VB) is a bioactive compound with potential antitumor properties, but its clinical application is limited by bioavailability.
- Developing targeted drug delivery systems can enhance the efficacy of natural compounds like VB against OSCC.
Purpose of the Study:
- To develop and evaluate a magnetic nanoparticle-based drug delivery system (VB-Fe3O4) for verbascoside (VB).
- To investigate the enhanced bioavailability, tumor-targeting capability, and antitumor efficacy of VB-Fe3O4 in OSCC.
- To elucidate the underlying molecular mechanisms of VB-Fe3O4 action in OSCC cells.
Main Methods:
- Synthesis and characterization of verbascoside-loaded magnetic nanoparticles (VB-Fe3O4).
- In vitro evaluation using human OSCC cell line (HSC-3), including apoptosis, proliferation, and invasion assays.
- In vivo assessment in OSCC transplanted and experimental metastasis tumor models.
- Analysis of the IL-6/STAT3 signaling pathway and key metastasis-related genes.
Main Results:
- VB-Fe3O4 exhibited superior tumor-targeting and drug accumulation compared to free VB.
- VB-Fe3O4 significantly inhibited OSCC cell proliferation, invasion, and induced apoptosis via the IL-6/STAT3 pathway.
- Intercellular cell adhesion molecule 1 (ICAM1) was identified as a primary target of VB.
- VB-Fe3O4 suppressed IL-6-induced STAT3 phosphorylation and downregulated metastasis-associated genes (VCAM1, MUC1, ezrin, MMP-9).
- Greater tumor suppression was observed in vivo with VB-Fe3O4 compared to free VB.
Conclusions:
- The VB-Fe3O4 nanoplatform effectively enhances the antitumor activity of verbascoside against OSCC.
- This system demonstrates precision delivery and molecular targeting, offering a promising therapeutic strategy for OSCC management.
- Targeting the IL-6/STAT3 pathway and ICAM1 presents a viable approach for combating OSCC progression and metastasis.
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