How does biological sex affect the physiological response to nanomaterials?

Abstract Nanomaterials are found in a wide range of industries from additives in consumer products, drug delivery vehicles, as well as environmental hazards. There is a growing body of evidence that suggests biological sex affects the host response to these nanomaterials. Given that male and female tissues do have distinct profiles of secreted factors, it is reasonable to expect that these adsorb to the surface of nanomaterials. These differences in the composition of the adsorbed biomolecular corona may induce different cellular responses based upon their biological sex. A sexual bias has been observed in the tissue-specific accumulation of nanomaterials, the extent of inflammation, and epigenetic modification induced by nanomaterials. While most of these studies involved exposure to environmental nanomaterials, there were limited examples that evaluated sexual biases related to nanomaterials for drug delivery, especially to the brain. A patient’s sex may influence the therapeutic or general host response to nanomaterials commonly used for biomedical applications. Herein, we begin with a description of the biomolecular corona as the effective interface between nanomaterials and biological systems. Then, the molecular aspects of sexual differentiation are presented regarding genetic factors, hormonal regulation, and mechanisms of processing xenobiotics, as the foundation from which to explore the sex-specific effects of nanomaterials.