Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Oral Microbiology Laboratory, Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Fellowship in Clinical Laboratory Sciences, Iran University of Medical Sciences, Tehran, Iran.
Photodiagnosis Photodyn Ther. 2021 Jun;34:102253. doi: 10.1016/j.pdpdt.2021.102253. Epub 2021 Mar 9.
Non-invasive sonodynamic therapy (SDT) is a new treatment modality that uses low-intensity ultrasound to activate a non-toxic sensitizing chemical agent for cancer therapy in a site-directed manner. This study aimed to investigate the anti-cancer effects of ultrasound combined with nano emodin transfersome (NET) on head and neck squamous cell carcinoma (HNSCC) cell lines.
A transfersome form of nano emodin as a novel sono-responsive nanomaterial was synthesized to enhance the accumulation and penetration of nanoparticles. iIn vitro experiments including hemolytic activity, cell proliferation, intracellular reactive oxygen species (ROS) generation, apoptosis induction, DNA fragmentation, and mRNA expressions of caspase 3 and 9 were conducted to explore the anti-cancer effects of NET-SDT on FaDu and CAL-27 cell lines.
Characterization tests showed the round and uniform morphology of NET with transfersome structure, resulting in a high drug-loading content and encapsulation efficiency. No significant hemolytic activity was observed (P > 0.05). Cytotoxicity gradually increased with increasing concentrations of NET, so that 10 × 10 g/L of NET plus 5 min ultrasound irradiation at a frequency of 1 MHz and ultrasonic intensity of 2 W/cm effectively killed 98.2 % and 97.3 % of FaDu and CAL-27 cell lines, respectively (P < 0.05). We found that ROS generation in NET-SDT was dose-dependent and the triggered apoptosis and caspase-3/9 gene expression levels were significantly enhanced as the concentration of NET increased (P < 0.05). No significant difference was found in the rate of apoptosis induction and gene expression between two cell lines.
Our data demonstrated that SDT with NET as a sonosensitizer can induce apoptosis and significantly decrease cell viability of HNSCC cell lines, which represents the role of NET-SDT as a potent anti-cancer modality.
非侵入性声动力学疗法(SDT)是一种新的治疗方式,它使用低强度超声激活无毒的敏化化学剂,以靶向方式进行癌症治疗。本研究旨在探讨超声联合纳米大黄素转铁蛋白(NET)对头颈部鳞状细胞癌(HNSCC)细胞系的抗癌作用。
合成了一种转铁蛋白形式的纳米大黄素作为新型声响应纳米材料,以增强纳米颗粒的积累和渗透。进行了体外实验,包括溶血活性、细胞增殖、细胞内活性氧(ROS)生成、细胞凋亡诱导、DNA 片段化以及 caspase 3 和 9 的 mRNA 表达,以探讨 NET-SDT 对 FaDu 和 CAL-27 细胞系的抗癌作用。
特征测试表明,NET 具有转铁蛋白结构,形态呈圆形且均匀,导致载药量和包封效率高。未观察到明显的溶血活性(P > 0.05)。细胞毒性随 NET 浓度的增加而逐渐增加,因此,10 × 10 g/L 的 NET 加 5 分钟频率为 1 MHz、超声强度为 2 W/cm 的超声辐射可分别有效杀死 98.2%和 97.3%的 FaDu 和 CAL-27 细胞系(P < 0.05)。我们发现,NET-SDT 中的 ROS 生成呈剂量依赖性,随着 NET 浓度的增加,触发的细胞凋亡和 caspase-3/9 基因表达水平显著增强(P < 0.05)。两种细胞系之间的细胞凋亡诱导率和基因表达没有显著差异。
我们的数据表明,NET 作为声敏剂的 SDT 可诱导 HNSCC 细胞系凋亡并显著降低细胞活力,这代表了 NET-SDT 作为一种有效的抗癌方式的作用。