Indeed, providing a biocompatible organic coating is often used to reduce toxicity of metal oxide nanoparticles. Polyethylene glycol (PEG) is a well-known biocompatible compound used for nanoparticle coating. As metal oxides react well with silanes, one way to coat your ZnO nanoparticles might be to let them react with PEG-silane. Some publications using this protocol are: DOI: http://dx.doi.org/10.101/j.jmmm.2012.01.032
Surly, the toxicity is depended on dimension, crystallite size and so on. How about their shape of the same size/surface area, rod, plate, sphere, etc. what shape is the most favoured and least toxic. Or there is nothing concerned to this point of view.
Look when you are talking about cytotoxicity of metallic nanoparticles then you should be very clear on concentration level as even for metallic nanoparticles may not show cytotoxicity below a critical concentration level. The otherway you can functionalize or encapsulate the metallic nanoparticles with some bio-degradable/bio-compatible polymer or even lipids .
I also work with metal oxide nanoparticles for biomedical applications. I have to agree with others above that coating with PEG is probably the best way to go as this stops proteins adsorbing on the surface of the nanoparticles in vivo and thus stops the body from recognising that there is an invading species. I've just had a quick search and found that catechols are good ligands towards ZnO, follow this link to a recent paper of my group, there you can find the protocol for conjugating catechols to PEG, this way you can then adsorb PEG directly on the surface of your nanoparticles:
http://pubs.acs.org/doi/abs/10.1021/la3012958
If you would prefer I can send you a step by step protocol if that would help?
Regarding your question on the role of morphology and crystallite size on cytotoxicity, our group has looked at these two parameters in ZnO and TiO2 nanostructures (eg, wires, particles, 3D urchin structures etc.) the findings show that both parameters are significant in these systems and can lead to cellular death in several different modes. One must also consider the solubility of Zn2+ in the cellular media. You can read more in the following two publications:
1. Effect of morphology of ZnO nanostructures on their toxicity to marine algae
Size of the particle is important in reducing the toxicity to cell. Following is an excerpt from my recently produced paper 'environmental concerns in antimicrobial finishing of textiles' (in press):
An important subject in evaluating the environmental effect of metal based antimicrobial finishes is to compare the various forms of metal particles. This is particularly useful when the two different forms of metal particles can produce similar antimicrobial performance. In such cases, the metal form producing the reduced effect to environment may be attractive as an environment- friendly finish. Silver- metal particle clusters showed antimicrobial activity comparable to Ag NPs effect. Stereo- type application of nanoparticles can be replaced with microparticles when the desired performance effects are achievable. For example, cellulose fiber substrate immersed in solution of Ag NO3 exhibited the desired performance effects [28].
An important factor that may be considered in chemical finishing is why to use nanoparticles when the desired effect was obtainable using an increased particle size. Difference was realized in comparison of silver particles and AgNPs in the ability to bind/ cross the cell membrane. Optimistically, an increased size of silver particle would reduce the tendency to cause such undesired effects. However, research studies are demanded to reveal the possible beneficial effects, obtainable through an increased size of metal particle, to environment and aquatic organism.