研究动态
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评估调节的细胞死亡方式作为一种有效的体外纳米毒性筛选工具:一项综述。

Assessing regulated cell death modalities as an efficient tool for in vitro nanotoxicity screening: a review.

发表日期:2023 Apr 21
作者: Anton Tkachenko, Anatolii Onishchenko, Valeriy Myasoedov, Svetlana Yefimova, Ondrej Havranek
来源: Experimental Hematology & Oncology

摘要:

纳米医学是纳米技术的一个快速发展领域。广泛使用新合成的纳米材料用于医疗应用的一个主要障碍是缺乏标准化的毒性筛选协议,以评估这些新型纳米材料的安全性。本文重点关注较少研究的纳米材料诱导的调节性细胞死亡(RCD)模式,包括脱屑、坏死样细胞死亡、炎症性细胞死亡和铁死亡,作为评估纳米材料安全性的体外工具。我们概述了响应于纳米材料暴露的介导这些 RCD 的机制的最新见解。所审阅的研究的综合数据表明,过氧化物酶(ROS)的过度产生和ROS介导的通路在纳米材料诱导的RCD激活中起着核心作用。另一方面,研究还表明,纳米材料的个体特性,包括大小、形状或表面电荷,可能确定具有相应RCD诱导的特定毒性通路。我们预计,评估RCD可以成为纳米毒理学中基于机制的筛选方法之一。除毒性评估外,评估纳米材料对坏死样细胞死亡、炎症性细胞死亡和铁死亡的促进能力,也可以同时为特定医疗应用提供有用的信息,例如它们的抗肿瘤潜力。此外,详细了解分子机制,促进纳米材料介导的免疫性RCD的形成,将极大地促进新型抗肿瘤纳米药物的开发。
Nanomedicine is a fast-growing field of nanotechnology. One of the major obstacles for a wider use of nanomaterials for medical application is the lack of standardized toxicity screening protocols for assessing the safety of newly synthesized nanomaterials. In this review, we focus on less frequently studied nanomaterials-induced regulated cell death (RCD) modalities, including eryptosis, necroptosis, pyroptosis, and ferroptosis, as a tool for in vitro nanomaterials safety evaluation. We summarize the latest insights into the mechanisms that mediate these RCDs in response to nanomaterials exposure. Comprehensive data from reviewed studies suggest that ROS (reactive oxygen species) overproduction and ROS-mediated pathways play a central role in nanomaterials-induced RCDs activation. On the other hand, studies also suggest that individual properties of nanomaterials, including size, shape, or surface charge, could determine specific toxicity pathways with consequent RCD induction as well. We anticipate that the evaluation of RCDs can become one of the mechanism-based screening methods in nanotoxicology. In addition to the toxicity assessment, evaluation of necroptosis-, pyroptosis-, and ferroptosis-promoting capacity of nanomaterials could simultaneously provide useful information for specific medical applications as could be their anti-tumor potential. Moreover, a detailed understanding of molecular mechanisms driving nanomaterials-mediated induction of immunogenic RCDs will substantially aid novel anti-tumor nanodrugs development.