Nanomaterials can cross the placental barrier and cause fetal damage

Jan 16, 2023 | Diseases & Drugs

The application of nanoparticles (NPs) and nanomedicine has increased dramatically in the last decade. However, there is growing concern about the safety of Nps in susceptible and vulnerable populations. Studies, which examined the fetotoxicity induced by Nps and the mechanisms involved have shown that nanomaterials can cross the placental barrier and cause fetal damage.

The term nanoparticles refers to particles having at least one dimension less than 100 nanometers. They are generally classified as natural or synthetic/anthropogenic NPs, depending on their origin. Another classification of NPs is their grouping into organic or inorganic nanoparticles. Organic nanoparticles include liposomes, dendrimers, micelles, etc. Metallic NPs, such as gold, iron, silver, aluminum, titanium oxide, and zinc oxide are examples of some of inorganic NPs.

Due to their small size and unique properties, nanomaterials can overcome biological tissue barriers. Translocation was initially described for primary barriers in the lung and gastrointestinal tract. Early evidence that nanomaterials can cross the placental barrier and induce developmental toxicity were obtained in animal studies, and the transfer was subsequently confirmed in perfusion studies of the human placenta.

About the studies

Due to their unique physicochemical properties, nanoparticles can directly cross the placenta and cause damage to the fetus, resulting in various fetal abnormalities. Possible transport pathways include passive diffusion, active transport, and endocytic pathway. Passive diffusion through the placenta is the predominant transport mechanism of small NPs.

The book chapter by Siddiqi NJ, et al analyzes in utero neurotoxicity of Nps. The authors emphasize that fetotoxicity of nanoparticles depends on their bioaccumulation, which in turn depends on the following factors: 1. Chemical composition, particle size, shape, surface change, and degree of agglomeration. The administration of higher doses of smaller NPs leads to their increased accumulation in placental and embryonic/fetal tissues. 2. Coating type, particle concentration, surface charge, zeta potential, solution pH, chemical characteristics, metal impurities, and degradation properties. 3. The anatomical and functional condition of the placenta  4. The period of exposure during gestation.

Maternal exposure to nanomaterials during gestation and fetotoxicity result in low birth weight, preterm birth, miscarriage, fetal resorption, morphological malformations, intrauterine growth retardation, and other embryo–fetal developmental abnormalities.

Gestational age is an important factor for the NPs-induced fetotoxicity, in particular for the neurodevelopmental sequelae. The developing brain is highly vulnerable to nanomaterials. Because of their small size, NPs with diameters of 1 to 100 nanometers cross the placental and the blood–brain barrier (BBB) and enter the central nervous system. Prior data demonstrated that smaller NPs cause more pronounced BBB breakdown, cerebral edema, neuronal injuries and up-regulation of glial fibrillary acidic protein in young animals.

Additionally, oxidative stress is one of the most important mechanisms of toxicity induced by NPs. Inflammation caused by the production of cytokines seems to be the second mechanism by which the NPs exert their cytotoxic effects. The majority of the resulting nervous tissue injuries are usually irreversible.

This peer-reviewed chapter was published in book Neurotoxicity – New Advances. Siddiqi NJ et al. In-Utero Neurotoxicity of Nanoparticles. In Neurotoxicity – New Advances, 2022, 10.5772/intechopen.94708 (Open Access)

A review article from Teng C, et al analyzed the fetotoxicity induced by nanoparticles and the mechanisms involved.

In this in-depth review, the authors discussed how the administration schedule, gestation stages, and maternal pathophysiological conditions affect fetotoxicity of NPs. They also analyzed nanotoxicity at the maternal–fetal interface, and the possible underlying mechanisms, including molecular mechanisms such as oxidative stress, DNA damage, apoptosis, and autophagy.

Maternal exposure to NPs during pregnancy may lead to severe genotoxic effects such as chromosomal aberrations, DNA strand breaks, DNA oxidative damage and micronucleus formation.

According to the authors, animal studies on nanotoxicity in pregnancy show that pregnant women should take precautions when using nano-based medicine or products. There is a tremendous need to better understand the mechanisms of developmental toxicity caused by nanomaterials.

This article was published in the scientific journal Nanomaterials. Teng C. et al. Fetotoxicity of Nanoparticles: Causes and Mechanisms. Nanomaterials 2021, 11, 791. (Open Access)

It should be noted here that previous research have shown that accumulation of nanoparticles in the reproductive organs of female mice seems to impair the development of oocytes and can compromise fertility.