The pharmaceutical nanofactory

Drug delivery is becoming one of the most often cited application of nanotechnology in the medical arena. For the kind of very toxic molecules that are used in cancer therapy, for example, substantial increases in effectiveness, and reductions in side-effects, can be obtained by wrapping up the molecule in a protective wrapper – a liposome, for example – which isolates the molecule from the body until it reaches its target. Drug delivery systems of this kind are already in clinical use, as I discussed here. But what if, instead of making these drugs in a pharmaceutical factory and wrapping them up in the nanoscale container for injection into the body, you put the factory in the delivery device, and synthesised the drug when it was needed, where it was needed, inside the body? This intriguing possibility is discussed in a commentary (subscription probably required) in the January issue of Nature Nanotechnology. This article is itself based on a discussion held at a National Academies Keck Futures Initiative Conference, which is summarised here.

One of the reasons for wanting to do this is to be able to make drug molecules that aren’t stable enough to be synthesised in the usual way. In a related problem, such a medical nanofactory might be used to help the body dispose of molecules it can’t otherwise process – one example the authors give is the condition phenylketonuria, a relatively common condition in which the amino acid phenylalanine, instead of being converted to tyrosine, is converted to phenylpyruvic acid, the accumulation of which causes incurable brain damage.

What might one need to achieve this goal? The first requirement is a container to separate the chemical machinery from the body. The most likely candidates for such a container are probably polymersomes, robust spherical containers self-assembled from block copolymers. The other requirements for the nanofactory are perhaps less easy to fulfill; one needs ways of getting chemicals in and out of the nanofactory, one needs sensing functions on the outside to tell the nanofactory when it needs to start production, one needs the apparatus to do the chemistry (perhaps a system of enzymes or other catalysts), one needs to be able to target the nanofactory to where one needs it, and finally, one needs to ensure that the nanofactory can be safely disposed of when it has done its work. Cell biology suggests ways to approach some of these requirements, for example one can imagine analogues to the pores and channels which transport molecules through cell membranes. None of this will be easy, but the authors suggest that it would constitute “a platform technology for a variety of therapeutic approaches”.