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Updated: Oct 10, 2025
Fabrication of Tongue Extracellular Matrix and Reconstitution of Tongue Squamous Cell Carcinoma In Vitro
Published on: June 20, 2018
A New Nanomaterial Based on Extracellular Vesicles Containing Chrysin-Induced Cell Apoptosis Through Let-7a in Tongue
Zhijing Yang1,2, Da Liu3, Hengzong Zhou2
1Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Jilin University, Changchun, China.
Abstract:
Although the therapeutic strategy showed significant improvement, the therapeutic effect was poor on metastases in tongue squamous cell carcinoma (TSCC) which is the most malignant tumor found in the head and neck. Chrysin, similar to the flavonoids, plays an antitumor role by regulating the expression of ncRNAs in many kinds of cancers. Compared to flavonoids, gold nanoparticles (AuNPs) provide a novel insight into inhibiting cancer cell growth via photothermal therapy (PPT) which is irradiated by near-infrared radiation (NIR). However, most flavonoids and AuNPs lack specificity of tumor in vivo. The extracellular vesicles (EVs) which were abundant with ncRNAs are isolated from the cellular supernatant fluid and have the ability to carry drugs or nanoparticles to improve specificity. In the present study, we aimed to synthesize a new nanomaterial based on EVs containing chrysin and analyzed cell apoptosis in TSCC cells. Our results demonstrated that EVs-chrysin were isolated from SCC9 cells that were treated with chrysin. To improve the therapeutic effect, AuNPs were carried by EVs-chrysin (Au-EVs). Compared to BGC823 and HCC-LM3 cells, the uptake of Au-EVs was specific in SCC9 cells. Moreover, Au-EVs combined with NIR enhanced cell apoptosis in TSCC cells. To confirm the role of miRNAs in cell apoptosis, the differentially expressed miRNAs between EVs-Con and EVs-chrysin were screened by RNA-seq. The results revealed that the let-7a-3p family, which acts as the tumor suppressor, was upregulated in EVs-chrysin compared to EVs-Con. Thus, let-7a-3p was screened in the apoptosis pathway that was associated with the p53 protein. Furthermore, compared to the Con group, Au-EVs combined with the NIR group effectively inhibited tumor growth in vivo via increasing the expression of let-7a-3p. Together, as a new nanomaterial, Au-EVs induced cell apoptosis and inhibited tumor growth by regulating let-7a-3p expression in TSCC.
Insights
This study developed gold nanoparticles (AuNPs) encapsulated in extracellular vesicles (EVs) loaded with chrysin. This novel nanomaterial, Au-EVs, specifically targets tongue squamous cell carcinoma (TSCC) and enhances apoptosis via photothermal therapy and let-7a-3p regulation.
Area of Science:
- Oncology
- Nanotechnology
- Molecular Biology
Background:
- Tongue squamous cell carcinoma (TSCC) exhibits poor therapeutic outcomes, especially for metastases.
- Chrysin and gold nanoparticles (AuNPs) show antitumor potential but lack tumor specificity.
- Extracellular vesicles (EVs) offer a promising platform for targeted drug and nanoparticle delivery.
Purpose of the Study:
- To synthesize and characterize a novel nanomaterial, Au-EVs, for targeted TSCC therapy.
- To evaluate the efficacy of Au-EVs combined with near-infrared radiation (NIR) in inducing TSCC cell apoptosis.
- To investigate the role of let-7a-3p in the therapeutic mechanism of Au-EVs.
Main Methods:
- Synthesis of chrysin-loaded EVs (EVs-chrysin) and AuNP-loaded EVs-chrysin (Au-EVs).
- Assessment of Au-EVs uptake specificity in TSCC cells (SCC9, BGC823, HCC-LM3).
- Evaluation of cell apoptosis induction by Au-EVs with NIR irradiation.
- RNA sequencing to identify differentially expressed miRNAs and investigation of let-7a-3p in the apoptosis pathway.
- In vivo tumor growth inhibition assay.
Main Results:
- Au-EVs demonstrated specific uptake in SCC9 TSCC cells.
- Au-EVs combined with NIR significantly enhanced TSCC cell apoptosis.
- RNA-seq revealed upregulation of tumor-suppressive let-7a-3p in EVs-chrysin.
- Au-EVs plus NIR inhibited tumor growth in vivo by upregulating let-7a-3p expression.
Conclusions:
- Au-EVs represent a novel, specific nanomaterial for TSCC therapy.
- The combination of Au-EVs and NIR effectively induces apoptosis and inhibits tumor growth.
- The therapeutic effect is mediated through the upregulation of let-7a-3p, highlighting its role in the p53-associated apoptosis pathway.
