The renowned immunologist and winner of the Nobel Prize for medicine, Paul Ehrlich, was a visionary, having already imagined at the very start of the 20th century that 'magic bullets' could be used to precisely target specific micro-organisms with toxins without flooding the body. It was to take three-quarters of a century before the first research on liposomes was published. In one fell swoop we were thrust into the future, towards nanotechnology! Significant challenges need to be overcome: an adequate vector has to be produced, the diseased cell has to be targeted and the active ingredient has to be protected, but must be released at the right time on target!

Ehrlich was already aware of the blind strength of some systemically-administered remedies which provoke toxic effects which can sometimes be as significant as the illness they are trying to treat. At this stage, he didn't know about antibiotics, which destroy the commensal flora alongside the pathogenic bacteria, nor anti-cancer chemotherapy which aims to destroy tumour cells, but at the cost of significant collateral damage.

The new science, called 'nanopharmacy' or 'nanomedicine' seeks to fine-tune 'transporters' which are capable of specifically targeting a diseased organ or tumour and, once there, of releasing the active ingredient which they are carrying. In some ways, this is a vital step for future progress: if we want to beat certain cancers by administering increasingly toxic molecules and/or at increasingly strong doses, this can only be possible if we are able to target them with precision. Because the best way to reach them is generally through the blood supply, the ideal would be to enable them to travel 'incognito' and only to activate them once they are in contact with their target.

Another avenue for research which may also benefit from nanopharmacy is gene therapy, because genetic material, as well as peptides or proteins would immediately be damaged in the body if they were injected without protection. It should be noted that gene therapy also uses viral vectors, which are not covered in the context of this article.

'We are thus facing a double challenge in nanopharmacy', states Géraldine Piel, Senior Researcher in the Laboratory of Pharmaceutical Technology of the University of Liège: 'targeting the diseased cell and protecting the active ingredient.' And, as we shall see, it is easier said than done!

Active or passive targeting

Let's start with targeting: it may be active or passive. If the target is identified/identifiable by biochemical or immunological characteristics, we can try to steer the active ingredient specifically towards it, by placing 'ligands' on the surface of the vectors, which can identify them. The target site may be a specific receptor which is over-expressed in the diseased tissue, specific small peptides, or quite simply folic acid (tumours often have several folate receptors). However, all this remains hypothetical: there are currently no vectors on the market which use active targeting.