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Engineered nanoparticles (ENPs) may cause toxicity if they cross various biological barriers and are accumulated in vital organs. Which factors affect barrier crossing efficiency of ENPs are crucial to understand. Here, we present strong data showing that various nanoparticles crossed biological barriers to enter vital animal organs and cause toxicity. We also point out that physicochemical properties of ENPs, modifications of ENPs in biofluid, and physiological and pathological conditions of the body all affect barrier crossing efficiency. We also summarized our limited understanding of the related mechanisms. On the basis of this summary, major research gaps and direction of further efforts are then discussed. ■ CONTENTS1. Introduction 1055 2. ENPs Crossed Biological Barriers 1055 3. Factors Affect the Barrier Crossing Efficiency of ENPs 1057 3.1. Properties of ENPs Determine the Interactions between ENPs and Biological Barriers 1057 3.2. Effects of Secondary Modifications of ENPs by Biofluid 1057 3.3. Effects of Physiological and Pathological Conditions of the Body 1057 4.

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The application of nanoparticles in consumer products and nanomedicines has increased dramatically in the last decade. Concerns for the nano-safety of susceptible populations are growing. Due to the small size, nanoparticles have the potential to cross the placental barrier and cause toxicity in the fetus. This review aims to identify factors associated with nanoparticle-induced fetotoxicity and the mechanisms involved, providing a better understanding of nanotoxicity at the maternal–fetal interface. The contribution of the physicochemical properties of nanoparticles (NPs), maternal physiological, and pathological conditions to the fetotoxicity is highlighted. The underlying molecular mechanisms, including oxidative stress, DNA damage, apoptosis, and autophagy are summarized. Finally, perspectives and challenges related to nanoparticle-induced fetotoxicity are also discussed.