石墨炔氧化物介导的光动力疗法通过增加细胞硬度来推动增强T细胞免疫反应。
Graphdiyne Oxide-Mediated Photodynamic Therapy Boosts Enhancive T-Cell Immune Responses by Increasing Cellular Stiffness.
发表日期:2023
作者:
Lejia Zhang, Kuangwu Pan, Siyuan Huang, Xiliu Zhang, Xinyu Zhu, Yi He, Xun Chen, Yuquan Tang, Lingyu Yuan, Dongsheng Yu
来源:
International Journal of Nanomedicine
摘要:
以纳米材料为基础的光动力疗法(PDT)已经广泛用于治疗癌症肿瘤。尽管在这个领域取得了显著的成就,但基于纳米材料的 PDT 对口腔鳞状细胞癌(OSCC)细胞的机械性质的内在影响尚不完全清楚。在这里,我们使用原子力显微镜(AFM)来测量 PDT 投射下的 OSCC 细胞的刚度,以评估 T 细胞介导的癌细胞杀伤效应。
本研究使用 AFM 评估 PDT 受试细胞的刚度。使用共聚焦激光扫描显微镜(CLSM)、膜固醇水平测试和 F-actin 细胞骨架评估评估了 graphdiyne 氧化物(GDYO)的光毒性。采用共培养系统评估了 CD8+ T 细胞(细胞毒性 T 淋巴细胞)的影响,展示了 PDT 如何调节癌细胞的机械性质并激活 T 细胞反应。GDYO 的抗肿瘤免疫治疗效果在小鼠异种移植模型中进一步评估。
GDYO 增加了肿瘤细胞的机械刚度,在激光下增强了 T 细胞细胞毒性和炎性细胞因子分泌(IFN-γ 和 TNF-α),并在体外阻止 OSCC 模型并通过特异性细胞毒性 T 细胞引发抗肿瘤免疫反应。这些结果强调 GDYO 是 OSCC 治疗的有希望的候选药物,可以改变 OSCC 细胞的机械作用力,并突破免疫抑制性的肿瘤微环境的障碍。我们的研究为基于纳米材料的抗肿瘤疗法提供了新的视角。©2023 张等。
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.© 2023 Zhang et al.