Biological responses to nanoparticles are temperature-dependant

201306047919620(Nanowerk Spotlight) When nanoparticles enter the human  body, for instance as part of a nanomedicine application, they come into  immediate contact with a collection of biomolecules, such as proteins, that are  characteristic of that environment, e.g. blood. A protein may become associated  with the nanomaterial surface during a protein-nanomaterial interaction, in a  process called adsorption.


The layers of proteins adsorbed to the  surface of a nanomaterial at any given time is known as the protein  corona (read more in our previous Nanowerk Spotlight: “Proteins  interact with ‘ultrasmall’ nanomaterials in unique ways”).   This protein coronas form a new surface on the nanoparticle that  actually would be ‘seen’ by biological entities (e.g. cells) rather than the  pristine surface of the synthesized nanoparticle itself. This is the reason why  biological responses to nanoparticles are strongly dependent to the type and  amount of associated proteins in the composition of the protein corona.

The type and amount of proteins in the corona composition is  strongly dependent on several factors, including physicochemical properties of  nanoparticles; protein source; and protein concentration. However, the effect of  temperature on the corona composition has not been investigated so far.

In new work, reported in the July 1, 2013 online edition of  ACS Nano (“Temperature: The ‘Ignored’ Factor at the NanoBio  Interface”), researchers have conducted a comprehensive study to show the  significant effect of temperature on corona composition.

The multi-institutional team, led by Morteza Mahmoudi, a  professor at Tehran University of Medical Sciences, who heads the Laboratory of  Nano-Bio Interactions, and Wolfgang Parak, a professor at the University of  Marburg, who heads the Biophotonics Group, investigated the influence  of the exposure temperature, ranging from 5 to 45°C, on the formation and  composition of the protein corona on magnetic nanoparticles as well as  nanoparticle-cell interactions.            adsorbed proteins on the surface of a nanoparticle


The  results indicate that the degree of protein coverage and the composition of the  adsorbed proteins on the nanoparticles’ surface depend on the temperature at  which the protein corona is formed. (Reprinted with permission from American  Chemical Society)

“Our findings are very important for the in vivo application of nanoparticle to humans,” Morteza Mahmoudi, a researcher at the  Nanotechnology Research Center at Tehran University of Medical Sciences, and  first author of the paper, tells Nanowerk. “The mean body temperature for  different individuals is in the range from 35.8 to 37.2 °C. Furthermore the  temperature varies for different parts of the body and the body temperature of  females is influenced by their hormonal cycle.

During the sleep the body  temperature decreases and manual work could lead to an increase. This means that  the body temperature for healthy humans varies in the range from 35 to 39°C and  can find a maximum of 41°C in the case of fever.”   “We have shown that changes in the incubation temperature can  cause significant effects in protein corona formation and composition, although  this is not necessarily always the case,” he adds.

“Temperature effects for the  nanoparticles investigated by us were especially pronounced in the  physiologically highly relevant temperature window of 37-41°C.”   The team hypothesized that, if protein adsorption onto the  surface of nanoparticles depends on the body temperature, it may also result in  a significant effect on the cellular uptake of nanoparticles in vivo.  Therefore they also assessed the effect of the temperature-dependent corona  composition on cellular uptake. They found, though, that their experimental data  does not allow for deriving a sharp conclusion about the correlation between the  temperature-dependence of protein corona formation and nanoparticle uptake.

These findings indicate that one can expect to have different  corona composition and, consequently, various biological responses to  nanoparticles for specific sites – and specific situation – of the human body.   “Our findings suggest that studies on the formation of a protein  corona on nanoparticles should be carried out at well-controlled temperatures to  enable comparison and reproduction of results from different laboratories,” says  Parak.

“We expect our results to apply to other classes of nanoparticles, such  as fluorescent or plasmonic nanoparticles, with similar surface  functionalization, although we have not proved this yet experimentally.”   Furthermore, since the area of protein corona is still in its  infancy, future work could be focused on potential ways to regulate corona  composition in vivo.                        By Michael Berger. Copyright © Nanowerk

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