ROS-Mediated Selective Killing Effect of Black Phosphorus: Mechanistic Understanding and Its Guidance for Safe Biomedical Applications
ROS-Mediated Selective Killing Effect of Black Phosphorus: Mechanistic Understanding and Its Guidance for Safe Biomedical Applications
复制标题
ROS介导的黑磷选择性杀伤作用：机理理解及其对安全生物医学应用的指导
DOI：
10.1021/acs.nanolett.0c01098
复制
发表时间：
2020-05-13
期刊：
影响因子：
10.8
通讯作者：
Tao, Wei
中科院分区：
文献类型：
--
作者：
Kong, Na;Ji, Xiaoyuan;Tao, Wei
黑磷（BP）基纳米材料在生物医学领域具有独特的优势和潜在的应用前景。然而，它们在生理系统中的生物学效应在很大程度上仍未被探索。在这里，我们系统地揭示了活性氧（ROS）介导的机制，用于通过基于BP的纳米片选择性杀死癌细胞。与正常细胞相比，用基于BP的材料处理可以在癌细胞中诱导更高水平的ROS，导致肿瘤细胞系中细胞骨架、细胞周期停滞、DNA损伤和凋亡的显著变化。我们发现，脂质过氧化物导致的超氧化物歧化酶活性降低可能是基于BP的纳米片在癌细胞中诱导的选择性较高的ROS产生的重要机制。此外，选择性杀伤作用仅发生在一定剂量范围内（本研究命名为“SK范围”）。一旦超过SK范围，基于BP的材料也可能在正常组织中诱导高ROS产生，导致正常器官中可检测到的DNA损伤和病理特征，并引起安全性问题。这些发现不仅揭示了基于BP的材料选择性杀死癌细胞的新机制，还为基于BP的治疗的安全使用提供了深刻的见解。
Black phosphorus (BP)-based nanomaterials have distinguished advantages and potential applications in various biomedical fields. However, their biological effects in physiological systems remain largely unexplored. Here, we systematically revealed a reactive oxygen species (ROS)-mediated mechanism for the selective killing of cancer cells by BP-based nanosheets. The treatment with BP-based materials can induce higher levels of ROS in cancer cells than in normal cells, leading to significant changes in the cytoskeleton, cell cycle arrest, DNA damage, and apoptosis in tumor cell lines. We revealed that the decreased superoxide dismutase activity by lipid peroxides could be an essential mechanism of the selectively higher ROS generation induced by BP-based nanosheets in cancer cells. In addition, the selective killing effect only occurred within a certain dosage range (named "SK range" in this study). Once exceeding the SK range, BP-based materials could also induce a high ROS production in normal tissues, leading to detectable DNA damage and pathological characteristics in normal organs and raising safety concerns. These findings not only shed light on a new mechanism for the selective killing of cancer cells by BP-based materials but also provide deep insights into the safe use of BP-based therapies.