In-Utero Neurotoxicity of Nanoparticles

*Nikhat J. Siddiqi, Sabiha Fatima, Bechan Sharma and Mohamed Samir Elrobh*

#### **Abstract**

The unique physicochemical properties of nanoparticles (NPs) make them widely used in cosmetics, medicines, food additives, and antibacterial and antiviral compounds. NPs are also used in therapy and diagnostic applications. Depending on their origin, the NPs are commonly classified as naturally occurring and synthetic or anthropogenic NPs. Naturally occurring nanoparticles can be formed by many physical, chemical, and biological processes occurring in all spheres of the earth. However, synthetic NPs are specifically designed or unintentionally produced by different human activities. Owing to their nano size and special properties, the engineered NPs can enter the human body through different routes such as dermal penetration, intravenous injection and inhalation. NPs may accumulate in various tissues and organs including the brain. Indiscriminate use of NP is a matter concern due to the dangers of NP exposure to living organisms. It is possible for NPs to cross the placental barrier, and adversely affect the developing fetus, posing a health hazard in them by causing neurodevelopmental toxicity. Thus, NP-induced neurotoxicity is a topic that demands attention at the maternal-fetal interface. This chapter summarizes the routes by which NPs circumvent the blood-brain barrier, including recent investigations about NPs' neurotoxicity as well as possible mechanisms involved in neural fetotoxicity.

**Keywords:** nanoparticle, neurotoxicity, placental barrier, blood-brain barrier

#### **1. Introduction**

The term nanoparticle (NP) refers to particles with at least one dimension less than 100 nanometers [1]. NPs are an essential part of earth's biogeochemical system, produced by many physical and chemical processes including different natural and human activities. They are commonly classified as naturally occurring and synthetic or anthropogenic NPs, depending on their origin. Synthetic or anthropogenic NPs can be further categorized into two types: incidental and engineered nanoparticles [2]. Naturally occurring nanoparticles can be formed by chemical, photochemical, mechanical, thermal, and biological processes occurring in all spheres of the Earth. NPs such as alumina, iron oxide, gold, sulfur manganese oxide, and so on derived from natural sources can be found in volcanic ash, fine sand, ocean spray, and even some biological matter [1]. Incidental nanoparticles are unintentionally produced as a byproduct of human day-to-day activities involving combustion process such as running diesel engines, large-scale mining, and even starting a fire.

On the other hand, the engineered or manufactured NPs such as silver, gold, zinc, metal oxides like manganese dioxide (MnO2), aluminum oxide Al2O3, titanium oxide (TiO2) of controlled shape, sizes, and compositions are specifically designed and deliberately synthesized by human beings [3]. Engineered NP include nonmetals like carbon nanotubes and quantum dots, polymers like chitosan, alginate, lipids like stearic acid, and metal sulfide like CuS, AgS, ZnS and so on [4]. Another classification of NP is their grouping into organic nanoparticles and inorganic nanoparticles. Organic nanoparticles include liposomes, dendrimers, micelles and so on. Examples of some of inorganic NP include metallic NP like gold, iron, silver, aluminum, titanium oxide (TiO2), and zinc oxide (ZnO). Nanomaterials can also be classified based on their size for example zero-dimension, one dimension, two dimension, and three dimensions [5]. Silver, gold, copper, and platinum are some of the most commonly used metals NP. Metal-based NPs can be easily conjugated with various functional groups, like polylysine, polyethylene glycol (PEG) or bovine serum albumin [6, 7].

The technological advancements of human society as well as progress in the field of nanotechnology have shown a sharp rise in consumer products that deliberately include synthetic nanoparticles [8]. This has resulted in high levels of exposure to many types of synthetic NPs, and it is likely that this trend will continue in future. The easiest place to find these nano-enabled products in our own homes is in health care products, cosmetics, and food additives. In the past decade, many companies have used ZnO and TiO2 NPs as sun block materials because these materials are very effective at absorbing UV radiation [9]. Some commonly used nanomaterials as food additives include silver, silicon dioxide (SiO2), titanium TiO2, and iron oxide (Fe2O3) [10]. Silver NPs are also commonly used as antibacterial and antiviral agents, while gold NPs are used for drug delivery, photothermal therapy and diagnostic applications, and polymeric NPs are used for controlled and targeted drug delivery [11].

Extensive use of engineered NP poses risk to human health. The health hazards are cause of concern in pregnant women and their unborn children. Therefore, it is important to study the toxic effect of NP on developing fetuses. In this chapter, we summarize the developmental toxicity of NP on the nervous system.

### **2. Factors affecting the toxicity of nanoparticles**

The embryonic toxicity of nanoparticles depends on their bioaccumulation, which in turn depends on the following [12]:


fullerene NPs have been demonstrated to enter cerebral microvessel endothelial cells and protect these cells by attenuating ROS-induced cellular damage, such as F-actin depolymerization [16].

