Biological Interactions of Ultrasmall Nanoparticles: What About the Corona?

Despite their potential for biological applications, the demonstrated tendency of nanoparticles (NPs) to accumulate in specific organs, as liver or spleen, in an uncontrolled fashion, still causes a considerable... [ view full abstract ]

Despite their potential for biological applications, the demonstrated tendency of nanoparticles (NPs) to accumulate in specific organs, as liver or spleen, in an uncontrolled fashion, still causes a considerable concern.^[1]  

However, it has been shown that for sizes below 3 nm certain NPs can display non-scalable properties^[2] and a different scenario in terms of biological interactions might be disclosed in respect of what is currently described for larger NPs.^[4] In vivo studies in mice, for example, showed the tendency of gold ultrasmall NPs (USNPs) to exhibit efficient renal clearance and almost no liver accumulation.^[5] This might not be due merely to their small core size. Generally, proteins present in the biofluids strongly interact with NPs forming long-lived biomolecular corona which, by altering the NPs surface, determine their final fate in the body.^[3]  Nevertheless, considering that most of the plasma/serum proteins present a hydrodynamic diameter up to 5 times the size of USNPs, can we still speak about biomolecular corona?

Investigation of USNPs-proteins complex is very challenging since the protocols normally used for larger NPs are ineffective. We obtained interesting insights on the bio-interactions of 5, 3 and 2 nm gold NPs (with a range of surface functionalisation) by using gel-electrophoresis. These assays, normally used to separate even small peptides, allowed to observe striking differences in the way NPs with 1 nm of size difference can interact with the biological environment. Below a certain size (also strongly depending on the surface chemistry of the particle) the long-lived NP-protein interactions could be nearly eliminate, suggesting that the corona might fluctuate rapidly, possibly leading to quite distinct biological outcomes compared to larger particles.

USNPs represent a new promising tool in nanomedicine, possibly not limited by unwanted organs accumulation but their interaction with biological fluids must be deeply investigated since it can be the key to understand their biodistribution and cell trafficking.

[1] ACS Nano 2017, 11, 5519–5529.

[2] Nanomedicine Nanotechnology, Biol. Med. 2016, 12, 1663–1701.

[3] Nat. Nanotechnol. 2012, 7, 779–786.

[4] Angew. Chemie - Int. Ed. 2017, 56, 4215–4218.

[5] Angew. Chemie - Int. Ed. 2011, 50, 3168–3172.