posted on 2024-01-01, 10:03authored byKiana Buttiens, Christy Maksoudian, Irati Perez Gilabert, Carla Rios Luci, Bella B. Manshian, Stefaan J. Soenen
Over the past decades, the medical exploitation of nanotechnology
has been largely increasing and finding its way into translational
research and clinical applications. Despite their biomedical potential,
uncertainties persist regarding the intricate role that nanomaterials
may play on altering physiology in healthy and diseased tissues. Extracellular
vesicles (EVs) are recognized as an important pathway for intercellular
communication and known to be mediators of cellular stress. EVs are
currently explored for targeted delivery of therapeutic agents, including
nanoformulations, to treat and diagnose cancer or other diseases.
Here, we aimed to investigate whether nanomaterials could have a possible
impact on EV functionality, their safety, and whether EVs can play
a role in nanomaterial toxicity profiles. To evaluate this, the impact
of inorganic nanomaterial administration on EVs derived from murine
melanoma and human breast cancer cells was tested. Cells were incubated
with subtoxic concentrations of 4 different biomedically relevant
inorganic nanoparticles (NPs): gold, silver, silicon dioxide, or iron
oxide. The results displayed a clear NP and cell-type-dependent effect
on increasing or decreasing EV secretion. Furthermore, the expression
pattern of several EV-derived miRNAs was significantly changed upon
NP exposure, compared to nontreated cells. Detailed pathway analysis
and additional studies confirmed that EVs obtained from NP-exposed
cells could influence immunological responses and cellular physiology.
Together, these data reveal that NPs can have wide-ranging effects
which can result in toxicity concerns or enhanced therapeutic potential
as a secondary enhanced effect mediated and enhanced by EVs.