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Nanoparticle safety: time to reconsider?

Advances in nanoparticle design have opened up a plethora of applications in medicine such as drug delivery and diagnosis. Therefore, it is of outmost importance to understand the impact of nanoparticles on immune response (not only in humans, but also in other species) and determine their environmental safety.

Health

Innate immunity is the first to be activated upon contact with a foreign object, whether it be a virus or a plastic particle. Innate immune cells and factors constitute the first line of defence at the barriers between the body and the external environment, and the mechanisms have been evolutionarily conserved in most species.

Assessing innate immune responses against nanomaterials

Undertaken with the support of the Marie Skłodowska-Curie programme, the PANDORA project studied the impact of nanoparticles in innate immunity. “The idea was to assess the toxicity of nanomaterials on the environment as a whole, including plants, terrestrial and marine invertebrates – and of course, on human health,” emphasises project coordinator Diana Boraschi. PANDORA researchers combined classical and state-of-the-art methodologies to examine the innate immune reaction upon exposure to nanomaterials. This included the interaction of nanoparticles with innate cells and symbiotic microbiota, as well as their effects at subcellular and molecular level and at the level of the entire organism. Partners investigated immune responses against the effects of iron, titanium, and cerium oxide nanoparticles with wide applications. Interestingly, they discovered unique elements and common features in the defensive responses of each organism. Following exposure to nanoparticles, immune responses led to a transient alteration of the organism’s homeostasis that resolved rapidly and did not cause long-term toxic effects. This indicates that the innate immune mechanisms can efficiently deal with foreign materials such as nanoparticles. However, at high doses and depending on their chemical composition, nanoparticles caused toxic effects. Interestingly, even in the absence of any initial immune responses against nanoparticles, the encounter with the innate immune system produced some kind of immune memory that shaped subsequent responses to other challenges.

Shaping the future design of nanoparticles destined for human applications

PANDORA's findings, suggesting that it is biologically impossible to predict nanoparticle toxicity purely based on design, provide the groundwork for the future design of safer nanoparticles for human use. “Safety of nanoparticles can be different for different organisms, at different doses, on different cells/tissue and for people in different health conditions. Thus, what is completely safe in a healthy young adult can have detrimental effects on an elderly individual with chronic pathologies,” emphasises Boraschi. Therefore, future efforts for biomedical applications of nanoparticles must focus on the selection of the appropriate administration route, dose and chemical composition, depending on the health status of the patient. Ongoing work on the mechanisms underlying these immune responses and their presence throughout living species will offer a holistic view on the safety of nanoparticles. Nonetheless, nanoparticles can be exploited to raise a beneficial innate memory. Given its non-specificity, this innate memory can be used in human beings to increase the efficacy of vaccines and for other kinds of therapeutic immunomodulatory approaches against a variety of diseases. In plants, induction of innate memory could be exploited to increase resistance to pests, and the same concept can be applied to invertebrates of commercial interest such as honeybees.

Keywords

PANDORA, nanoparticle, innate immunity, immune response, toxicity, innate memory, toxic effects, nanomaterials

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24 February 2021