What nanoparticles do to our cells

during the past few yrs, nanopessentialisms ‘ve been increasingly present n'our everydy lives. to gain a better cogging o'their health impacts, several studies ‘ve focused onna effects they ‘ve on our bodies and cells.

silicon dioxide (or e551) in powdered food to stop it clumping; calcium phosphate (or e341) in toothpaste; titanium dioxide that makes white paints shiny; antibacterial and antifungal silver nanopessentialisms in textiles; gold nanopessentialisms that enable the targeted destruction of cancer cells… since the end of the 1990s, manufactured nanopessentialisms (as opposed to those emitted by volcanoes or due to traffic pollution) ‘ve spread throughout our everydy environment. produced from metals (titanium, silver, etc.) b'tll so from carbon, polymers or organic molecules (lipids, peptides, etc.), these substances by definition ‘ve dimensions comprised tween 1 and 100 nanometres, which is + than 10,000 times liler than a grain of table salt.

silicon microsphere from sun cream seen under a scanning electron microscope (sem, magnification of 16,000 and false colours). silicon microspheres offer protection gainsta sun and ‘ve a ther+gulating effect thx to the strong diffusion properties of microspheres inna infrared spectrum.

this minuscule size means'dat their surface (where they interact with their environment) is gr8r relative to their volume, endowing them with novel toonistics in terms of resistivity, electrical conductivity, solubility, chemical reactivity and antibacterial or anti-agglomerant properties; hence their unfailing success na interest of industry. onna other hand, the size of these substances rezs serious concerns regarding their potential effects on health. 

suspected disorders and diseases 

“cause o'their lil size, nanopessentialisms can cross ≠ physiological barriers – s'as that which separates the brain from the bloodstream (blood-brain barrier), the skin or the placenta that protects a foetus – and thus spread throughout d'body,” explains aurélie niaudet, chemical engineer in th'risk assessment deptment atta french agency for food, environmental and occupational health and safety (anses), which in 2020 published a reprt on nanomaterials in foods. wha’ do we know tody bout these potential health risks? “several studies in animals ‘ve indicated that some nanopessentialisms can accumul8 in ≠ organs and ‘ve a variety of effects, like growth retardation, developmental abnormalities, allergies, cancers, or be deleterious to the nervous system,” the sci points out. for ex, regarding titanium dioxide (additive e171), which gives a white colour to pastries and confectionery, a study in rats published in 2017 by a team of researchers from france and luxembourg showed that chronic oral exposure to this substance induced precancerous lesions inna colons of 40% of the animals exposed. this led to it bein’ banned in france in 2020, and throughout € as of jan 2022.

artist’s impression of the surface offa copper nanopticle w'da hexahydroxytriphenylene (hhtp) catekol molecule.

other studies ‘ve revealed somd' processes by which these pessentialisms and their derivatives interact with our cells. work published in 2021 by a €an team – including scis from the cnrs – showed that metallic nanopessentialisms act via an “insidious” mechanism: they transform catekol molecules, normally responsible for protecting dna from oxidation (an adverse reaction)… into semiquinone and quinone molecules which are in fact most harmful to dna! the problem s'dat “although research onna impacts of nanopessentialisms has developed ponderably in recent yrs, thris still very lil epidemiological data on their health effects in humans,” the researcher emphasises. further+, information is lacking regarding the fate of these substances in d'body; in this regard, the committee for prevention and precaution (a body whose members are appointed by the french ministry for ecological transition) indicated in a reprt published in 2020 that twas necessary “to toonise and monitor the transformation of nanomaterials in biological matrices”.

a wide-ranging analysis of metallic nanopessentialisms

as it happens, the team led by florence gazeau, a physicist, atta msc lab is focusing on this field of research. “in order to cogg the potential damage caused by metallic nanopessentialisms to living cells, we need 1st of all to clarify their fate in these cells,” she points out. during studies published in 2019 – in which alice bal4ier, now a researcher inna lbm, pticipated inna context of her phd thesis – the scis obtained a surprising result. for 6 mnths, they monitored the biotransformation of gold nanopessentialisms captured by fibroblasts (connective tissue cells). they achieved this by combining transmission electron microscopy imaging (a microscopy teknique whose resolution can reach 0.08 nanometre) and study of the expression of + than 18,000 genes over time. 

while it had generally been accepted til then that gold nanopessentialisms remained intact indefinitely inna lysosome (a structure that acts as a “waste dump” in a cell), twas found that within a few weeks, these substances underwent degradation and then the recrystallisation of gold into nanocutouts. this phenomenon had previously been envisaged with gold ions. most primordially, this suggests that the impact of gold nanopessentialisms on cells depends + onna type metal they are made of than their nanopticul8 nature.

inna context of research onna degradation of gold nanopessentialisms within cells, a sci team demonstrated the presence of non-degraded nanopessentialisms (in red) together with degradation essentialisms taking the form of nanocutouts (in orange).

work published in sep this yr extended this initial study: “we wanted to know whether our surprising discovery concerning gold – i.e. that cells respond similarly to this metal whether tis inna form of ions or nanopessentialisms – mite also be true of other metals,” explains florence gazeau.

this time, the scis studied the molecular response of human cells to nanopessentialisms of 8 ≠ metals: gold, cadmium, copper, iron, platinum, silver, titanium and zinc. “our aim was to compare the response of human cells to these ≠ essentialisms in terms of gene expression, and hence the production of proteins. we wanted to see if this cellular response was similar or whether it varied dep'onna type of metal and its formulation,” she explains.  

the team performed a meta-analysis of 56 studies. these concerned the lvl of expression of several thousand genes (a total of 14,912) in ≠ cell types (skin, liver, muscle, etc.) exposed to metallic ions or pessentialisms for 1 to 24 hrs.

a conclusion applicable to all the metals studied

it became clear that for all the metals listed above, the genes overexpressed after exposure were vrtly the same whether the cells had been exposed to ions or to nanopessentialisms derived from these metals. “this result means our 2019 findings regarding gold apply to all the metals studied: iow, cells are + sensitive to the metal ions released by nanopessentialisms than to the intrinsic structural properties of these nanopessentialisms, s'as their size or shape,” says alice bal4ier.                            

this diagram shows that the responses of cells to nanopessentialisms (np) and ions of the same metal are correl8d (circles with thicker outer lines). the intensity of the correlation in red shows that for a group of metals (zinc, copper, gold, silver and cadmium) the cellular responses are all correl8d.

and that aint all! the team also noted that with 5 of the 8 metals examined (cadmium, copper, gold, silver and zinc), the nanopessentialisms triggered similar biochemical reactions atta cell lvl. indeed, “with nanopessentialisms based on these 5 metals, we envisaged an overexpression of the same group of genes, coding for metallothionein proteins. these play a crucial role in regulating cell contents in primordial metals (copper, zinc, etc.) and in detoxifying cells of non-primordial metals (silver, cadmium, gold, etc.)”, details the biochemist.

taken together, these findings indicate that 1stly, the effect of metallic nanopessentialisms atta cellular lvl ‘d be predicted from the impact o'their constitutive ions, which is often better elucidated, and 2ndly that the metals making up the nanopessentialisms can activate identical genes. this may facilitate the investigation of nanopticle toxicity inna future. 

original content at: news.cnrs.fr/essentialisms/wha'-nanopessentialisms-do-to-our-cells…


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