Last updated March 22, 2018 at 11:35 am
Nanomedicines must take sex into account.
The difference between males and females is deeper than even movies and reality TV might have us believe. We’re talking cellular level.
New research from North America has found that cells from men and women respond differently to the reprogramming techniques used to enhance the ability of the cells to differentiate into a greater variety of cell types.
This helps fill an important information gap and may eventually help researchers more safely and effectively produce nanomedicines that take sex into account.
According to Dr Morteza Mahmoudi, from Brigham and Women’s Hospital (BWH), the number of medical nanoparticle technologies making it from the lab to clinical trials is much lower that might be expected and a large part of the reason is the number of “overlooked factors at the nanobio interface”.
With colleagues from BWH, Stanford University, McGill University and University of California, Berkeley, Mahmoudi had previously identified cell type, cell shape and incubating temperature as factors influence how well cells take up nanoparticles, and sex was next on the list.
Cells are awash in biomolecules
The team incubated nanoparticles with human amniotic stem cells (hAMSCs) which were extracted from the amniotic layer of placenta attached to male and female foetuses. They found that female cells had significantly higher uptake of nanoparticles than male cells.
In the body, cells are awash in a wide range of biomolecules, including paracrine factors, which are small proteins that can interact with the surface of nanoparticles. The study found that paracrine factors varied between male and female cells: of the 63 paracrine factors measured, 14 showed major differences. These differences can affect the biological identity of nanoparticles and thus alter their interaction with the cells.
The team also found important differences in organisation, distribution and morphology of actin filaments in male and female hAMSCs. These filaments act like tiny tendrils that wrap around particles and engulf them.
“These differences could have a critical impact on the administration of nanoparticles,” said Mahmoudi. “If nanoparticles are carrying a drug to deliver, different uptake could mean different therapeutic efficacy and other important differences, such as safety, in clinical data.”
The team also tested nanoparticle absorption for other kinds of human cells, including fibroblasts from donors of older ages and found significant differences. Interestingly, the team found that male fibroblast cells had higher levels of uptake than female fibroblast cells. They also saw differences in the shape of the cells’ mitochondria and endoplasmic reticulum structure among other differences.
“What we’re seeing is that cell type is also going to be critical. If we’re trying to deliver a chemotherapeutic drug, the cell type we are targeting as well as the sex of the patient may influence how well the drug is delivered and absorbed,” said Mahmoudi.
The paper published in ACS Nano.