Nanotoxicity and the importance of being earnest.

In the process of advancing new technologies, in particular those intended to improve human health, it is not an uncommon observation that its proponents glorify the benefitswith directnesswhile addressing the unresolved matters in vaguer terms. More often, however, real progress requires at the very least the ability to fully appreciate overt or hidden dangers of new medical treatments. In a sense, it is needed when seeing a spade also to call it a spade. We believe that the successful development of nanomedicines is in no exception to this need. A spade, however, is an easily visible and identifiable object where little sophistication is required to assess its potential use or associated dangers. As tools, nanomedicines are widely different with regard to the ease in such assessment. The National Institutes of Health defines nanomedicine as a form of nanotechnology performed at the molecular scale [1]. It was and remains one of the big challenges of the past and present centuries to visualize – or “see” – the structure of biological macromolecules. The dimensions of nanoparticles are on par with the dimensions of a large plasma protein. Several lines of investigation suggest that the topological features of the particles permit interaction with proteins in non-trivial ways [2–6]. While these interactions are likely to be important in the adverse reactions to the particles, means of characterizing them are scarce. For instance, although mass spectrometry may serve to address what protein species are deposited on the surface of plasma-exposed particles [7], the colloidal nature of these particles limits the application of other methodologies of biochemistry. Imaging of nanoparticles is also checked by the size, when this is below the Abbe diffraction limit excluding several types of microscopical analyses that in other cases have been helpful, for example, in understanding the tissue distribution of particulate material. In principle, one would think that the link between molecular shape and toxicology established through many years of pharmacological research contributes a straightforward rational extendable to cover nanoparticles as well. However, the work by Leszczynski et al. shows that no simple ways are likely to exist of formalizing the assessment of the toxicological hazards presented by nanostructured materials. Only more complex computational methodologies are ways to resolve this issue safely [8,9]. The spade is easily designed to make its way into the ground. By contrast, once inside the body the nanomedicines find themselves in a hostile environment, where considerable ingenuity in design is required to keep the therapeutic potential intact. In itself thismaynot present a toxicological problem, but a considerable body of evidence points that it is the immune system of the host incapacitating their function [10,11]. The immune response in this situation is akin to a type of hypersensitivity reaction, whichmay trigger violent inflammatory responses. This way, materials such as carbon nanotubes may cause harm in the