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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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Applications of nanomaterials cause a general concern on their toxicity when they intentionally (such as in medicine) or unintentionally (environment exposure) enter into the human body. As a special subpopulation, pregnant women are more susceptible to nanoparticle (NP)-induced toxicity. More importantly, prenatal exposures may affect the entire life of the fetus. Through blood circulation, NPs may cross placental barriers and enter into fetus. A cascade of events, such as damage in placental barriers, generation of oxidative stress, inflammation, and altered gene expression, may induce delayed or abnormal fetal development. The physicochemical properties of NPs, exposure time, and other factors directly affect nanotoxicity in pregnant populations. Even though results from animal studies cannot directly extrapolate to humans, compelling evidence has already shown that, for pregnant women, caution must be taken when dealing with nanomedicines or NP pollutants.

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