Institute for Superconducting and Electronic Materials, Australian Institute for Innovative Materials, University of Wollongong, 2500 North Wollongong, New South Wales, Australia.
Illawarra Health and Medical Research Institute, University of Wollongong, 2500 Wollongong, New South Wales, Australia.
ACS Appl Mater Interfaces. 2021 Jan 20;13(2):2204-2217. doi: 10.1021/acsami.0c17326. Epub 2021 Jan 5.
In this article, we demonstrate that specifically engineered oxide nanoparticles (NPs) have the potential to act as theranostic materials that are able to generate or prevent oxidative stress through their oxi-redox activity in various types of malignant and nonmalignant cells. The oxi-redox activity is related to the type and presence of surface defects, which is modified with appropriate synthesis conditions. In the present work, we used MDA-MB-231 and MCF-7 human breast cancer cells and nonmalignant MCF-10A human breast cells to demonstrate how controlled oxidative stress mediated by specifically nanoengineered indium tin oxide (ITO) NPs can selectively induce cell death in the cancer cells while reducing the oxidative stress in the normal cells and supporting their proliferation. The ITO NPs are also promising nanotheranostic materials for cancer therapy and contrast agents because of their multimodal imaging capabilities. We demonstrate that the synthesized ITO NPs can selectively increase the generation of reactive oxygen species (ROS) in both breast tumor cell lines, resulting in activation of apoptosis, and can also greatly suppress the cellular proliferation in both types of tumor cells. In contrast, the ITO NPs exhibit ROS scavenging-like behavior, significantly decreasing the ROS levels in MCF-10A cells exposed to the additional ROS, hydrogen peroxide (HO), so that they protect the proliferation of nonmalignant MCF-10A cells from ROS damage. In addition, fluorescent microscopy images revealed that the ITO NPs emit strong fluorescence that could be used to reveal their location. Moreover, computed tomography imaging demonstrated that the ITO NPs exhibited a comparable capability toward anatomical contrast enhancement. These results suggest that the synthesized ITO NPs have the potential to be a novel selective therapeutic agent with a multimodal imaging property for anticancer treatment.
在本文中，我们证明了经过特殊设计的氧化物纳米粒子（NPs）具有作为治疗诊断一体化材料的潜力，通过其在各种类型的恶性和非恶性细胞中的氧化还原活性，可以产生或预防氧化应激。氧化还原活性与表面缺陷的类型和存在有关，而表面缺陷的类型和存在可以通过适当的合成条件来修饰。在本工作中，我们使用 MDA-MB-231 和 MCF-7 人乳腺癌细胞和非恶性 MCF-10A 人乳腺癌细胞来证明如何通过专门纳米工程化的氧化铟锡（ITO）NPs 控制的氧化应激来选择性地诱导癌细胞死亡，同时减少正常细胞中的氧化应激并支持其增殖。ITO NPs 还具有作为癌症治疗和对比剂的多功能治疗诊断一体化材料的潜力，因为它们具有多模态成像能力。我们证明了合成的 ITO NPs 可以选择性地增加两种乳腺癌细胞系中活性氧（ROS）的产生，导致细胞凋亡的激活，并且还可以大大抑制两种类型的肿瘤细胞的细胞增殖。相比之下，ITO NPs 表现出清除 ROS 的行为，大大降低了暴露于额外 ROS（过氧化氢（HO））的 MCF-10A 细胞中的 ROS 水平，从而保护非恶性 MCF-10A 细胞的增殖免受 ROS 损伤。此外，荧光显微镜图像显示，ITO NPs 发出强烈的荧光，可用于显示其位置。此外，计算机断层扫描成像显示，ITO NPs 具有相似的解剖对比增强能力。这些结果表明，合成的 ITO NPs 具有成为具有多模态成像特性的新型选择性治疗剂的潜力，可用于癌症治疗。
