Dear Alexandra

If you are using in-vitro cultures, try using phytohemagglutinin-M or concavalin-A to stimulate the lymphocytes. It might enhance the endocytotic activity of lymphocytes....

http://www.sciencedirect.com/science/article/pii/0014482777902890

Thank you for your answer! Will such stimuli also increase the accumulation of the drug inside the lymphocytes?

Well, i think if the lymphocyte is metabolically active and the drug you are using can get metabolized there are less chances of getting accumulated....

I suspect that the drug is not metabolized since it interchilates directly with the cells' DNA (it's doxorubicin).

Endocytosis is a regulated process. Receptors are internalised upon binding to the specific ligand, they also have a constitutive "tonic" endocytosis but this is a minor efect compared with ligand stimulation. Are you sure that your nanoparticles enter by endocytosis? and not by pinocytosis? One possibility is to add ligands to the surface of your particles so that they can interact with specific receptors and trigger the internalization of the whole complex. This also could work with specific antibodies.

You can modulate endocytosis by treating your cells with hypo-/hyper-tonic media. The effect on endocytosis is cell type specific, maybe have a look in Apodaca 2002, "Modulation of membrane traffic by mechanical stimuli". Good luck. Clara

For drugs like doxorubicin, the problem is often efflux by PGP rather than uptake. There are many papers on this. You could look at J Pharmacol Exp Ther. 2008 Jan;324(1):95-102. Epub 2007 Oct 18 as one example.

Dear Mr Maxfield,

To my knowledge, the PgP and ABC cassette pumps are upregulated only in neoplastic cells hence the efflux of DOX from healthy cells should be limited.

Dear Mrs Lubeseder-Martellato,

Sounds promising, I will have a look at it thanks!

Increase temperature, or slightly increase pH of medium, or target for receptor-mediated endocytosis. If it is a B lymphocyte perhaps use anti-dec205 (recent Blood paper).