Hospital of Stomatology, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Guangzhou, People's Republic of China.
Int J Nanomedicine. 2023 Feb 15;18:797-812. doi: 10.2147/IJN.S392998. eCollection 2023.
Nanomaterial-based photodynamic therapy (PDT) has been commonly used for the treatment of cancerous tumors. Despite significant achievements made in this field, the intrinsic impact of nanomaterials-based PDT on the mechanical properties of oral squamous cell carcinoma (OSCC) cells is not entirely understood. Here, we used atomic force microscopy (AFM) to measure the stiffness of OSCC cells subjected to PDT in co-culture systems to evaluate the T cell-mediated cancer cell-killing effects.
In this study, AFM was used to assess the stiffness of PDT-subjected cells. The phototoxicity of graphdiyne oxide (GDYO) was assessed using confocal laser scanning microscopy (CLSM), measurements of membrane cholesterol levels, and assessments of the F-actin cytoskeleton. A co-culture system was used to evaluate the effects of CD8 T cells (cytotoxic T lymphocytes), demonstrating how PDT modulates the mechanical properties of cancer cells and activates T cell responses. The antitumor immunotherapeutic effect of GDYO was further evaluated in a murine xenograft model.
GDYO increased the mechanical stiffness of tumor cells and augmented T-cell cytotoxicity and inflammatory cytokine secretion (IFN-γ and TNF-α) under laser in vitro. Furthermore, GDYO-based PDT exerted inhibitory effects on OSCC models and elicited antitumor immune responses via specific cytotoxic T cells.
These results highlight that GDYO is a promising candidate for OSCC therapy, shifting the mechanical forces of OSCC cells and breaking through the barriers of the immunosuppressive tumor microenvironment. Our study provides a novel perspective on nanomaterial-based antitumor therapies.
基于纳米材料的光动力疗法（PDT）已被广泛用于治疗癌症肿瘤。尽管在该领域取得了重大进展，但基于纳米材料的 PDT 对口腔鳞状细胞癌（OSCC）细胞机械性能的内在影响尚未完全了解。在这里，我们使用原子力显微镜（AFM）来测量共培养系统中接受 PDT 的 OSCC 细胞的硬度，以评估 T 细胞介导的癌细胞杀伤效应。
在这项研究中，使用 AFM 来评估 PDT 处理过的细胞的硬度。使用共聚焦激光扫描显微镜（CLSM）评估了石墨炔氧化物（GDYO）的光毒性，测量了膜胆固醇水平，并评估了 F-肌动蛋白细胞骨架。使用共培养系统来评估 CD8 T 细胞（细胞毒性 T 淋巴细胞）的影响，表明 PDT 如何调节癌细胞的机械性能并激活 T 细胞反应。进一步在小鼠异种移植模型中评估了 GDYO 的抗肿瘤免疫治疗效果。
GDYO 在体外激光下增加了肿瘤细胞的机械硬度，并增强了 T 细胞的细胞毒性和炎症细胞因子（IFN-γ 和 TNF-α）的分泌。此外，基于 GDYO 的 PDT 通过特异性细胞毒性 T 细胞对 OSCC 模型发挥抑制作用并引发抗肿瘤免疫反应。
这些结果表明 GDYO 是治疗 OSCC 的一种有前途的候选药物，改变了 OSCC 细胞的机械力，并突破了免疫抑制肿瘤微环境的障碍。我们的研究为基于纳米材料的抗肿瘤治疗提供了新的视角。
