A New Nanomaterial Based on Extracellular Vesicles Containing Chrysin-Induced Cell Apoptosis Through Let-7a in Tongue Squamous Cell Carcinoma

Zhijing Yang; Da Liu; Hengzong Zhou; Boqiang Tao; Lu Chang; Huimin Liu; Haoming Luo; Dongxu Wang; Weiwei Liu

doi:10.3389/fbioe.2021.766380

A New Nanomaterial Based on Extracellular Vesicles Containing Chrysin-Induced Cell Apoptosis Through Let-7a in Tongue Squamous Cell Carcinoma

Front Bioeng Biotechnol. 2021 Nov 26:9:766380. doi: 10.3389/fbioe.2021.766380. eCollection 2021.

Authors

Zhijing Yang^{1

2}, Da Liu³, Hengzong Zhou², Boqiang Tao¹, Lu Chang¹, Huimin Liu¹, Haoming Luo³, Dongxu Wang², Weiwei Liu¹

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Jilin University, Changchun, China.
² Laboratory Animal Center, College of Animal Science, Jilin University, Changchun, China.
³ Department of Pharmacy, Changchun University of Chinese Medicine, 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.

Keywords: cell apoptosis; extracellular vesicles; gold nanoparticles; let-7a; tongue squamous cell carcinoma.