Department of Microbiological and Biochemical Pharmacy & The Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Adv Exp Med Biol. 2018;1048:71-84. doi: 10.1007/978-3-319-72041-8_5.
In the past decades, nanoparticles have been widely used in industry and pharmaceutical fields for drug delivery, anti-pathogen, and diagnostic imaging purposes because of their unique physicochemical characteristics such as special ultrastructure, dispersity, and effective cellular uptake properties. But the nanotoxicity has been raised over the extensive applications of nanoparticles. Researchers have elucidated series of mechanisms in nanoparticles-induced toxicity, including apoptosis, necrosis, oxidative stress, and autophagy. Among upon mechanisms, autophagy was recently recognized as an important cell death style in various nanoparticles-induced toxicity, but the role of autophagy and its related cellular and molecular mechanisms during nanoparticles-triggered toxicity were still confusing. In the chapter, we briefly introduced the general process of autophagy, summarized the different roles of autophagy in various nanoparticle-treated different in vitro/in vivo models, and deeply analyzed the physicochemical and biochemical (cellular and molecular) mechanisms of autophagy during nanoparticles-induced toxicity through listing and summarizing representative examples. Physicochemical mechanisms mainly include dispersity, size, charge, and surface chemistry; cellular mechanisms primarily focus on lysosome impairment, mitochondria dysfunction, mitophagy, endoplasmic reticulum stress and endoplasmic reticulum autophagy; while molecular mechanisms were mainly including autophagy related signaling pathways, hypoxia-inducible factor, and oxidative stress. This chapter highlighted the important role of autophagy as a critical mechanism in nanoparticles-induced toxicity, and the physicochemical and biochemical mechanisms of autophagy triggered by nanoparticles might be useful for establishing a guideline for the evaluation of nanotoxicology, designing and developing new biosafety nanoparticles in the future.
在过去几十年中，由于纳米粒子具有特殊的超微结构、分散性和有效的细胞摄取特性等独特的物理化学特性，已被广泛应用于工业和制药领域，用于药物输送、抗病原体和诊断成像。但是，由于纳米粒子的广泛应用，其纳米毒性问题也引起了人们的关注。研究人员已经阐明了纳米粒子诱导毒性的一系列机制，包括细胞凋亡、细胞坏死、氧化应激和自噬等。在这些机制中，自噬最近被认为是各种纳米粒子诱导毒性中的一种重要的细胞死亡方式，但是自噬在纳米粒子触发毒性过程中的作用及其相关的细胞和分子机制仍然存在混淆。在本章中，我们简要介绍了自噬的一般过程，总结了自噬在不同的体外/体内模型中对各种纳米粒子处理的不同作用，并通过列举和总结代表性实例，深入分析了自噬在纳米粒子诱导毒性过程中的物理化学和生物化学（细胞和分子）机制。物理化学机制主要包括分散性、粒径、电荷和表面化学；细胞机制主要集中在溶酶体损伤、线粒体功能障碍、线粒体自噬、内质网应激和内质网自噬；而分子机制主要包括自噬相关信号通路、低氧诱导因子和氧化应激。本章强调了自噬作为纳米粒子诱导毒性的关键机制的重要作用，纳米粒子引发的自噬的物理化学和生物化学机制可能有助于建立纳米毒理学评价的指导方针，为未来设计和开发新的生物安全纳米粒子提供参考。
