We made a pilot study with N=2 mice per group to test biodistribution of rhodamine 6G-loaded silica nanoparticles functionalized with PEG, at 1.5h, 6h and 24h. We used GFP detector in IVIS Spectrum 200 imaging system and normalized fluorescence efficiency to control organs average, as a ratio (N=2 as well).
We expected to find high accumulation in liver, spleen and lung, possibly decreasing with time, but surprisingly we cannot see any rhodamine signal in liver at any time when compared to control organ. We made sure the biliary vesicle was not present and liver was properly washed. Signal in spleen is not very high either. Nevertheless, lung signal at 1.5 hours is 5-fold the controls signal, decreasing in time and disappearing at 24h.
We know optical imaging is not the most sensitive technique to assess nanoparticle biodistribution, but we can clearly see rhodamine signal in lung. What could possibly be going on in liver and spleen? Could their color or opacity cause any quenching of the signal? I've found this article detecting rhodamine in liver using the same equipment as we do (Article Conjugation of curcumin-loaded lipid nanoemulsions with cell...
) so I guess it is not a matter of quenching...Do we have the best and most biocompatible nanoparticles ever? I don't think so! But we need an explanation for the lack of liver uptake...
Dear Esperanza Medina-Gutiérrez ,
I noticed that in the paper you referred to, they made use of a Rhodamine labelled lipid (Rhodamine-DSPE), see also enclosed file for the corresponding supplement info. This is a clear hydrophobic form of Rhodamine. You used Rhodamine R6 which is reasonably soluble in water (and at physiological pH cationic). I’ve seen reports where they suggest that this cationic molecule binds to (mitochondrial) membranes.
I am no expert in this type of research, but could it be that the difference in results has something to do with the difference between these Rhodamine molecules? And would it make sense to wait longer before you start testing? Or try to use a more hydrophobic Rhodamine, like Rhodamine B (https://www.scbt.com/p/rhodamine-b-base-509-34-2)?
Anyway, hope this helps somewhat.
Best regards.
Dear Rob Keller,
Thank you very much for your kind answer!, I did not realise there was such a difference!
Still, to avoid undesired interactions that could lead to different biodistributions (nanoparticles like ours are usually uptaken by RES organs), or dye degradation, in our case rhodamine is loaded *inside* the nanoparticle. Thus, it is not exposed to plasma, so I do not believe it is a matter of solubility (at least, not rhodamine-related)...
I'll keep on researching!
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