ACS Nano. 2018 Mar 14. doi: 10.1021/acsnano.7b06212. [Epub ahead of print]

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

Serpooshan V^1,2, Sheibani S³, Pushparaj P⁴, Wojcik M⁵, Jang AY⁶, Santoso MR⁶, Jang JH⁷, Huang H⁵, Safavi-Sohi R⁸, Haghjoo N⁹, Nejadnik H¹⁰, Aghaverdi H¹¹, Vali H³, Kinsella JM⁴, Presley J³, Xu K^5,12, Yang PC⁶, Mahmoudi M^6,11.

Abstract

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.