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Comment by rgejman | Hacker News Reader

I am very pessimistic about the likelihood of this being a non-toxic visualization strategy in mice or men. These "microdiamonds" are unlikely to clear the kidneys, leading to kidney toxicity. This is the problem with all ≥ nanoscale molecules, with the exception of very long ones such as nanotubes which can pass longitudinally through the kidney slit diaphragms.

Many a great drug (and visualization agent) has failed because of kidney toxicity.

It's surprising that there are no MDs on the team.

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You are correct in the fact that the kidney's are one route of clearance for small agents that are injected. However, these are typically small molecule agents or particles on the lower size range at a couple nms in diameter. To reference a highly sited scientific article from Chemical Rev (Chem. Rev. 2010, 110, 2921–2959), "At 8 nm, observations have been made that hepatic uptake begins to dominate clearance routes, and by 10-12 nm the reticuloendothelial excretion route becomes the dominant route for clearance."

These nanodiamonds range in size from 15-100nm, so the kidneys will not be their primary route of clearance. It is also crucial to note that with any nanoparticle development, coating is a major factor in its biodistribution behavior. Coatings can and have been designed in more recent work regarding nanomedicine that minimize various biodistribution issues.

If they are in fact small enough to escape via biliary excretion, that would be great. But just skimming the literature it looks like they can accumulate and persist for weeks in the liver—a situation which would suggest hepatotoxicity is another problem (Zhu et al 2012 in "Theranostics" -- never heard of that journal but paper looks 'ok').

Coatings won't help this problem unless you can somehow change the shape of the crystal to fit through the slit OR get it to cross into the renal luminal space via transcytosis or excreted more efficiently in the biliary tree. All difficult propositions.

I really hope novel techniques like this work but this particular on seems very problematic. If I were you I would complete a serious set of toxicity studies very early on to make sure this isn't a fish that's dead in the water.

Edits: clarifying the points

Toxicity concerns are always utmost to consider when developing tools for the clinic! Thus far, all studies regarding nanodiamonds have shown biocompatibility and non-toxicity. Coming from a research background and having done a number of in vivo studies myself, these studies we plan to repeat with each targeted version of the nanodiamond (particle + ligand such as antibody) before reaching the clinic. To clarify, we are at the pre-clinical level currently.

Non-invasive circulating cancer cell (CTC) screening from blood samples seems to have the most promise.

(disclaimer: I run a project in this area)

You should get in touch with the folks at Denovo Sciences. They're working on a platform for CTC capture and identification.

http://denovosciences.com/

Agreed, for now. Caveats TBD. In particular issues of access (e.g. astrocytomas, non-metastatic bladder) and identity (what does it mean to be a CTC? A known driver mutation? We know that some tissues are littered with such mutations...)

Which project? CTC screening is fascinating. Could you please point me to some good introductory papers/reading?

I am on vacation right now, without my literature archive in arms reach, but from recent publications you may be interested in the whole-exome single cell sequencing work from Lohr et al.

http://www.nature.com/nbt/journal/v32/n5/abs/nbt.2892.html

There is also an overview editorial in that issue of Nature Biotechnology.

http://www.nature.com/nbt/journal/v32/n5/full/nbt.2897.html

I remember seeing reviews in Lab Chip and Nat Rev Clinical Oncology recently.

http://pubs.rsc.org/en/Content/ArticleLanding/2014/LC/C3LC50...

http://www.nature.com/nrclinonc/journal/v11/n3/full/nrclinon...

The introduction sections of those papers should give you plenty of references to read. It's a good idea to look into the devices/methods used to enrich CTCs from blood prior to screening; Toner's devices based (in part) on EPCAM expression, and the CellScreen device (size/morphology), in particular.

Thanks!

that is actually one area of applications we are exploring! I'd love to have a chat with you about it.

Sounds great! I will have to try to contact you/Bikanta when I return from vacation.

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