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close"..engineered nanomaterials [.] are able to translocate across the cellular membrane"
Posted by raphavisses on 11 Dec 2014 at 09:35 GMT
Sorry to offer a comment not so much on the paper, but on its context. From the author's summary:
"The increasing applications of nanotechnology in medicine rely on the fact that engineered nanomaterials, such as diagnostic and therapeutic nanoparticles, are able to translocate across the cellular membrane and reach their site of action without toxic effects."
This is repeated in a very large number of papers. However, it is an urban myth (or a science myth). Please provide one example of an existing medical application of nanotechnology that rely on nanoparticles translocating across the cellular membrane.
Endocytosis remain the main mechanism of entry for nanoparticles into cells (leading to particle being constrained inside intracellular vesicles and therefore unable to reach cytosolic targets), and while there are multiple papers claiming direct entry, the evidence is often weak or indirect, and there is certainly no existing approved medical application based on this phenomenon.
RE: "..engineered nanomaterials [.] are able to translocate across the cellular membrane"
zoecournia replied to raphavisses on 11 Dec 2014 at 13:20 GMT
Dear Raphael,
Thanks for the comment. If you read our abstract sentence carefully, you will notice that we write "...therapeutic nanoparticles, are able to translocate across the cellular membrane...". Translocation is a general word in the context of reaching the intracellular environment and it does not tell us anything about the mechanism of translocation. Endocytosis is a specific mechanism of translocation across a membrane, whereas "direct translocation" is another mechanism, which is based on diffusion.
I agree with you that currently there is very little evidence as to whether a NP could translocate directly across a cellular mechanism and this is exactly what we set out to investigate with CGMD simulations. You will notice from our computed free energy barrier that NP translocation in the case of 50% cholesterol, which is close to the concentration of cholesterol in dendritic cells (used in van Lehn et al etc), is too large and I postulate that direct translocation may not be the method of NP translocation in this specific systems. We are currently investigating other mechanisms that may be probable.