One reason nanotechnology and medicine potentially make a good marriage is that the size of nano-objects is very much on the same length scale as the basic operations of cell biology; nanomedicine, therefore, has the potential to make direct interventions on living systems at the sub-cellular level. A paper in the current issue of Nature Nanotechnology (abstract, subscription required for full article) gives a very specific example, showing that the size of a drug-nanoparticle assembly directly affects how effective the drug works in controlling cell growth and death in tumour cells.
In this work, the authors bound a drug molecule to a nanoparticle, and looked at the way the size of the nanoparticle affected the interaction of the drug with receptors on the surface of target cells. The drug was herceptin, a protein molecule which binds to a receptor molecule called ErbB2 on the surface of cells from human breast cancer. Cancerous cells have too many of these receptors, and this affects the communications between different cells which tell cells whether to grow, or which marks cells for apoptosis – programmed cell death. What the authors found was that herceptin attached to gold nanoparticles was more effective than free herceptin at binding to the receptors; this then led to reduced growth rates for the treated tumour cells. But how well the effect works depends strongly on how big the nanoparticles are – best results are found for nanoparticles 40 or 50 nm in size, with 100 nm nanoparticles being barely more effective than the free drug.
What the authors think is going on is connected to the process of endocytosis, by which nanoscale particles can be engulfed by the cell membrane. Very small nanoparticles typically only have one herceptin molecule attached, so they behave much like free drug – one nanoparticle binds to one receptor. 50 nm nanoparticles have a number of herceptin molecules attached, so a single nanoparticle links together a number of receptors, and the entire complex, nanoparticles and receptors, is engulfed by the cell and taken out of the cell signalling process completely. 100 nm nanoparticles are too big to be engulfed, so only that fraction of the attached drug molecules in contact with the membrane can bind to receptors. A commentary (subscription required) by Mauro Ferrari sets this achievement in context, pointing out that a nanodrug needs to do four things: successfully navigate through the bloodstream, negotiate any biological barriers preventing it from getting it where it needs to go, locate the cell that is its target, and then to modify the pathological cellular processes that underly the disease being treated. We already know that nano-particle size is hugely important for the first three of these requirements, but this work directly connects size to the sub-cellular processes that are the target of nanomedicine.