Change is inevitable. Nothing in the environment stands still, and this requires entities living in it to adapt. All organisms on planet Earth, including humans, possess the inherent ability to adapt to changing environments. In fact, cells are equipped with molecular machineries that allow them to respond to stimuli. At first, a quick acute response is activated to limit damage, but if the stimulus persists, the cell will reprogram itself through epigenetic mechanisms such as DNA methylation, histone modifications, and transcription factors binding to regulatory genomic regions. These rewiring mechanisms increase plasticity in gene regulation and improve the chances of survival.

Richard Feynman's 1959 lecture “There is plenty of room in the bottom”¹  initiated the field of nanotechnology by inviting his colleagues to manipulate materials at the nanoscale level. Today, nanomaterials  between 1 and 100 nm are widely used in products, but their potential risks and the appropriate assessment methods are still uncertain. Particulate matter exposure is nothing new to living beings, as they have been exposed to particulate matter throughout Earth's eons (e.g. from volcanoes eruptions). Nonetheless, modern human-made nanoparticles present an unprecedentedly persistent exposure, especially through air pollution. How do cells and organisms readjust to this changing environment?

In our research, we discovered a molecular epigenetic mechanism common to several species throughout the tree of life that mediates the long-term cellular responses to particulate matter. Our study proved that the regulation from a specific family of transcription factors (C₂H₂-ZNF) mediates the molecular adaptation to a variety of nanoparticles, in species with various levels of organismal complexity. C₂H₂-ZNFs are a well known conserved family throughout evolution, controlling stress responses, immune functions and chromatin remodeling, responsible for regulating responses to other exogenous agents, such as viruses and abiotic stress. 

A new dimension to assess the health and environmental impact of nanomaterials across species 

Regulatory agencies and research institutions have now long studied at various levels the effects of intentional and unintentional nanoparticulate exposures on humans and the environment, including the molecular dimension. Both nanoparticles’ size and their composition confer them unique properties which are not comparable to other chemicals.

Currently, toxicologists must test each nanomaterial individually to evaluate its health and environmental implications, but the available tests are species-specific and focus mainly on acute responses. With the widespread use of nanoparticles, faster and more reliable methods are needed to assess the potential toxicity across multiple species and for longer-term consequences.

Our investigation helps to fill this gap in the field, paving the way for a new generation of tests that can simultaneously investigate the impact of nanoparticles across species, contributing to the reduction of animal experimentation and streamlining the process to multiple ENMs (engineered nanomaterials) with disparate physicochemical characteristics.  

Which are the implications of this discovery?

Predicting the long-term effects of particulate  exposure

Our discovery offers a novel way to study long-term responses of cells, tissues and entire organisms to many particulate exposures. The possibility that nanoparticles could somehow epigenetically reprogram biological systems provides an additional dimension to assess health and environmental impact. In fact, it is already well known that exposures to environmental factors contribute to disease susceptibility by impacting the epigenome. In this sense, our results highlight the need to correctly identify chronic effects of nanoparticles’ intentional and unintentional exposure, with possibly important epidemiological implications.

One step closer to Planetary Health

Our findings revealed that a wide range of species across the tree of life respond to particulate exposure activating molecular regulations mediated by an ancestral epigenetic mechanism, which is present also in non-specialized cells and in simpler organisms. This is an important step towards the end of the scientific dichotomy that so far has focused on either human or environmental implications of the ENMs production, and instead embraces the interconnectedness and interdependence of the health of humans, animals, and the environment, towards a planetary health model. 

A link between nanoparticles and immunity

Our epigenetic model suggests that the response to nanoparticles may be a conserved function of the innate immune system, highlighting the link between particulate exposure and immunomodulation. This link is particularly relevant in light of recent events, such as the COVID-19 pandemic, where basal immune activation determines disease prognosis. Patients in more polluted areas are at higher risk of severe and lethal forms of the disease. Air pollution has also been identified as a driving cause of cancer in non-smokers by keeping the immune system activated for extended periods.

Overall, our research offers a promising step towards a more comprehensive understanding of the impacts of particulate matter on biological systems and the environment, while contributing to the development of faster and more reliable toxicity tests which are closer to planetary health models.