Have you considered co-functionalizing your gold nanoparticles with thiolated PEG molecules? PEG can definitely help reduce non-specific interactions. I imagine the PEG may reduce these interactions, while the oligonucleotides may still allow the nanoparticles to carry out their function. Furthermore, take a look at this paper in ACS: http://pubs.acs.org/doi/abs/10.1021/nn3035155

PEG can help reduce protein adsorption. There is commercial lipoic acid-PEG-maleimide molecule you can purchase to still be able to use thiolated DNA on top of the PEG coating. However, I would always expect a protein corona around DNA coated particles, irrespective of the specific DNA sequence. There is a lot of work on protein corona out there, just search for it.

Thanks for the answers. Can I use thiolated PEG  for attaching thiolated dna oligo.

How to get rid of protein corona.What is the chemistry of using  lipoic acid-PEG-maleimide Ron. Do you any good paper who will explain all the chemistry of functionalizing gold for oligo attachment.

The point is that if you use a medium supplemented with serum you will always have a protein corona...is the nature of the nanoparticle itself to be very sticky to proteins. If you use a serum free medium probably you won't have any corona..but in a non-physiological situation. You can find a lot of articles aboutthe concept of hard and soft corona.

try coating with osmium tetraoxide

 hi, valentina.it`s difficult to grow cell without serum.