Chen Min-Hua, Hanagata Nobutaka, Ikoma Toshiyuki, Huang Jian-Yuan, Li Keng-Yuan, Lin Chun-Pin, Lin Feng-Huei
Institute of Biomedical Engineering, National Taiwan University, Taipei 10051, Taiwan; Nanotechnology Innovation Station, National Institute for Materials Science, Tsukuba 3050047, Japan.
Nanotechnology Innovation Station, National Institute for Materials Science, Tsukuba 3050047, Japan.
Acta Biomater. 2016 Jun;37:165-73. doi: 10.1016/j.actbio.2016.04.004. Epub 2016 Apr 6.
UNLABELLED: Recently, photodynamic therapy (PDT) is one of the new clinical options by generating cytotoxic reactive oxygen species (ROS) to kill cancer cells. However, the optical approach of PDT is limited by tissue penetration depth of visible light. In this study, we propose that a ROS-enhanced nanoparticle, hafnium-doped hydroxyapatite (Hf:HAp), which is a material to yield large quantities of ROS inside the cells when the nanoparticles are bombarded with high penetrating power of ionizing radiation. Hf:HAp nanoparticles are generated by wet chemical precipitation with total doping concentration of 15mol% Hf(4+) relative to Ca(2+) in HAp host material. The results show that the HAp particles could be successfully doped with Hf ions, resulted in the formation of nano-sized rod-like shape and with pH-dependent solubility. The impact of ionizing radiation on Hf:HAp nanoparticles is assessed by using in-vitro and in-vivo model using A549 cell line. The 2',7'-dichlorofluorescein diacetate (DCFH-DA) results reveal that after being exposed to gamma rays, Hf:HAp could significantly lead to the formation of ROS in cells. Both cell viability (WST-1) and cytotoxicity (LDH) assay show the consistent results that A549 lung cancer cell lines are damaged with changes in the cells' ROS level. The in-vivo studies further demonstrate that the tumor growth is inhibited owing to the cells apoptosis when Hf:HAp nanoparticles are bombarded with ionizing radiation. This finding offer a new therapeutic method of interacting with ionizing radiation and demonstrate the potential of Hf:HAp nanoparticles in tumor treatment, such as being used in a palliative treatment after lung surgical procedure. STATEMENT OF SIGNIFICANCE: Photodynamic therapy (PDT) is one of the new clinical options by generating cytotoxic reactive oxygen species (ROS) to kill cancer cells. Unfortunately, the approach of PDT is usually limited to the treatment of systemic disease and deeper tumor, due to the limited tissue penetration depth of visible light (620-690nm). Here we report a ROS-enhanced nanoparticle, hafnium-doped hydroxyapatite (Hf:HAp), which can trigger ROS when particles are irradiated with high penetrating power of ionizing radiation. The present study provides quantitative data relating ROS generation and the therapeutic effect of Hf:HAp nanoparticles in lung cancer cells. As such, this material has opened an innovative window for deeper tumor and systemic disease treatment.
未标注：最近，光动力疗法（PDT）是一种新的临床选择，通过产生细胞毒性活性氧（ROS）来杀死癌细胞。然而，PDT的光学方法受到可见光组织穿透深度的限制。在本研究中，我们提出一种ROS增强纳米颗粒，铪掺杂羟基磷灰石（Hf:HAp），当纳米颗粒受到高穿透能力的电离辐射轰击时，它是一种能在细胞内产生大量ROS的材料。Hf:HAp纳米颗粒通过湿化学沉淀法制备，相对于HAp主体材料中的Ca(2+)，Hf(4+)的总掺杂浓度为15mol%。结果表明，HAp颗粒能够成功掺杂Hf离子，形成纳米尺寸的棒状形状且具有pH依赖性溶解性。使用A549细胞系的体外和体内模型评估电离辐射对Hf:HAp纳米颗粒的影响。2',7'-二氯荧光素二乙酸酯（DCFH-DA）结果显示，暴露于γ射线后，Hf:HAp可显著导致细胞内ROS的形成。细胞活力（WST-1）和细胞毒性（LDH）测定均显示一致结果，即A549肺癌细胞系随着细胞内ROS水平的变化而受损。体内研究进一步表明，当Hf:HAp纳米颗粒受到电离辐射轰击时，由于细胞凋亡，肿瘤生长受到抑制。这一发现提供了一种与电离辐射相互作用的新治疗方法，并证明了Hf:HAp纳米颗粒在肿瘤治疗中的潜力，例如可用于肺部手术后的姑息治疗。 重要性声明：光动力疗法（PDT）是一种新的临床选择，通过产生细胞毒性活性氧（ROS）来杀死癌细胞。不幸的是，由于可见光（620 - 690nm）的组织穿透深度有限，PDT方法通常局限于全身性疾病和较深肿瘤的治疗。在此我们报告一种ROS增强纳米颗粒，铪掺杂羟基磷灰石（Hf:HAp），当颗粒受到高穿透能力的电离辐射照射时，它能触发ROS。本研究提供了与Hf:HAp纳米颗粒在肺癌细胞中产生ROS及治疗效果相关的定量数据。因此，这种材料为较深肿瘤和全身性疾病的治疗打开了一扇创新之窗。
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