Effect of Cell Sex on Uptake of Nanoparticles: The Overlooked Factor at the Nanobio Interface

Cellular uptake of nanoparticles (NPs) depends on the nature of the nanobio system including the solid nanocomponents (e.g., physicochemical properties of NPs), nanobio interfaces (e.g., protein corona composition), and the cellular characteristics (e.g., cell type). In this study, we document the role of sex in cellular uptake of NPs as an overlooked factor in nanobio interface investigations. We demonstrate that cell sex leads to differences in NP uptake between male and female human amniotic stem cells (hAMSCs), with greater uptake by female cells. hAMSCs are one of the earliest sources of somatic stem cells. The experiments were replicated with primary fibroblasts isolated from the salivary gland of adult male and female donors of similar ages, and again the extent of NP uptake was altered by cell sex. However, in contrast to hAMSCs, uptake was greater in male cells. We also found out that female versus male amniotic stem cells exhibited different responses to reprogramming into induced pluripotent stem cells (iPSCs) by the Yamanaka factors. Thus, future studies should consider the effect of sex on the nanobio interactions to optimize clinical translation of NPs and iPSC biology and to help researchers to better design and produce safe and efficient therapeutic sex-specific NPs.