Hi All,
I am wondering why Nanoparticles with conjugated mABs on their surface as targeting agents are successfully taken up by cells at the receptor site through Receptor-Mediated Endocytosis but using the same mAB alone as a therapy inhibits the receptor without being taken up at all.
I don't understand why they would not either both be taken up or neither be taken up.
Any help is greatly appreciated!
EF
Hi Eduard
You have raised a very interesting question indeed. It is worth exploring further. My theory is this. When anti-EGFR antibody binds to the EGFR receptor, it triggers Fc receptor mediated cytotoxicity involving natural killer cells and cytotoxic T lymphocytes. So why it doesn't happen when the antibody is linked to a nanoparticle. I suspect that the nanoparticle binds to the part of the antibody molecule (possibly Fc receptor) that is involved in recruiting mediator cells (NK/T cells) ie obscuring the binding domain. Hence, it does not result in cytotoxicity but is taken up inside the cell by RME. Does it make sense? Have you tested your observation by using a dye doped NP and fluorescent labelled antibody under confocal microscope? I would be interested to know what you find. Good luck
If I understand your question, why are Ab coated beads taken up, but the Ab by itself is not? Ab coated beads have multiple antibodies which will bind and crosslink receptors on the cell surface. Crosslinking of many cell surface receptors is enough to induce endocytosis. A single antibody may bind up to two receptors, at best. This is not enough to induce endocytosis, but may effectively block the normal action of the surface receptor. If the cell you are targeting has Fc receptors it may be possible they are also contributing to the endocytosis. The same effect applies. If you crosslink multiple Fc receptors you will induce endocytosis.
As per as my knowledge Nanoparticles with conjugated mABs on their surface as targeting agents are successfully taken up by cells because it prevent the pre maturation degradation (RES). Moreover nanoparticle carrier binds to the part of the antibody molecule (possibly Fc receptor) that is involved in recruiting mediator cells (NK/T cells) ie obscuring the binding domain.
Muttuswamy, I have not made this observation personally, just something from the literature I was curious about. Thank you all for your responses!
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