Thread by @raphavisses

This highly cited 2010 @acsnano article reports the first MD simulations of gold nanoparticles with lipid membranes.
pubs.acs.org/doi/full/10.10…

Let's look at how they justify the research.

They say "applications have been growing over the past 5 years" and give references [1-5], but ref 1-5 just make similar promises. 10 years later these applications which were supposed to be growing still do not exist.

The whole thrust of this influential article is that direct penetration of nanoparticles through membranes is important. What evidence do they provide that it exists in the first place?

First paragraph of intro:
"In most of these bioapplications, the NPs are required to pass cell plasma membranes either by endocytosis(8) or by direct penetration to reach target cellular compartments, during which significant toxic effects may be induced to the cells.(9)"

Great, so ref 9 is going to give us evidence of direct penetration and associated toxic effects, right?
Well, here is ref 9:
dx.doi.org/10.1126/scienc…

Ref 9 is a "special viewpoint" in @ScienceMagazine (commonly called a review) on drug delivery systems. It talks about drug delivery systems but says precisely zero, nada, nothing on membrane penetration by nanoparticles.

Amusing observation; still 1st para of intro. Nanoparticles is a bit of a wooly term & that is sometimes useful.
So at the beginning of the paragraph
"look, NPs greater than polycation at delivering DNA"
End of paragraph
"important to optimize NPs [cite review abt polycations]"

Let's now move to the second paragraph. Surely ref to evidence of direct penetration will now be provided.

Yes!

"it is found that cationic and anionic AuNPs follow different internalization pathways (endocytosis or penetration of cell membrane) to enter cells.(13)"

Well, no.
"Although these results might support the claims in refs 25 and 26 [i.e. penetration], +info is still needed to figure out the exact pathways of internalization for positively charged colloidal particles."
pubs.acs.org/doi/10.1021/nl…

Ref 13 provides zero evidence of direct penetration. Nor does it pretend to do so. It does not even look at intracellular localisation.

Let's keep going. We would not have an article doing MD simulations of a phenomenon that does not exist. That would be ridiculous. Surely they are going to provide the evidence.

"Interestingly, surface-structure-regulated anionic AuNPs can bypass endocytosis without overtly disrupting cell membranes.(17) However, the mechanism of AuNP uptake is still poorly understood."

🙄
I have dealt with ref 17 in some details here.
raphazlab.wordpress.com/2012/11/23/str…

That's it. Then comes the argument for theoretical work:

"The lack of atomic-level details on AuNP−cell membrane interactions prevent us from gaining an in-depth understanding of the observed phenomena."

But there is no observed phenomena. No evidence.

This theoretical study has prompted many many more theoretical studies of this phenomenon which does not exist.

The end.

please unroll @threadreaderapp