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Sex affects how nanoparticles behave.

The function of a cell is largely considered its defining characteristic, suggesting that for example, one human amniotic stem cell (hAMSC) would behave on the whole much like another. However, as Joseph Matthew Kinsella, John Presley, Ke Xu, Phillip Chung-Ming Yang, and Morteza Mahmoudi and colleagues point out in their recent ACS NANO, there have been several reports over the past decade highlighting distinctions between the same cell type - in terms of functions such as cell secretions and signalling pathways – depending on the gender of the host the cell is taken from.

Responses to nanoparticles depend on cell sex.

Credits: ACS NANO

The researchers suggest that the effects of gender may be a contributing factor preventing lab successes in nanomedicine translating effectively into clinical use.

Gender bias

By comparing how cells taken from males and females interact with commercial quantum dots using flow cytometry, confocal microscopy, and transmission electron microscopy, the researchers were able to demonstrate that gender can significantly affect quantum dots uptake. Further investigation of secretions revealed differences in the levels of 14 cytokines that may affect the protein corona that forms on the quantum dots, which influences interactions with the cell. Studies of actin filament structure also revealed differences for the different genders, suggesting further mechanisms involved in quantum dot uptake that may contribute to the bias in uptake.

A bias towards greater quantum dot uptake was found in hAMSCs taken from the amniotic sac of female foetuses compared with those from males. hAMSCs are some of the earliest sources of stemcells. The researchers also found gender-based differences in quantum dot uptake by somatic primary fibroblast cells from male and female adults, although here uptake was greater for male fibroblast cells.

The researchers also investigated gender-based differences in the uptake of the nanoscale Sendai virus, which researchers use to transfect cells like hAMSCs into "induced pluripotent stem cells" (ipSCs). There is a lot of interest in ipSCs because they can differentiate into any other type of cell, a useful trait for medical treatments to replace damaged or diseased cells. Despite differences in the uptake mechanism, Kinsella and colleagues found a significant increase in Sendai virus uptake of hAMSCs and resulting ipSCs in hAMSCs from females compared with those from male hosts.

"We suggest that cell sex is an overlooked factor in research relevant to the nanobio interface," they conclude in their report. They add, "Our continuous reports of the overlooked factors and future progress in the field of nanobio interfaces might have the potential to facilitate successful clinical translation of nanoparticles."

Full details are reported in ACS Nano, DOI:10.1021/acsnano.7b06212.

By Anna Demming. Posted: Mar 17, 2018.

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