Dendrimers have been designed to deliver drugs on target

Scientists have long known that one of the most effective ways to treat cancer is to target anti-cancer drugs specifically at cancerous cells. A number of targeting methods have been explored, most of which involve using natural recognition molecules such as antibodies, with varying degrees of success. A team of researchers from the University of Michigan, Ann Arbor, US, has now come up with a novel method, which involves using synthetic tree-like polymers known as dendrimers.

A dendrimer is a macromolecule in which a number of chains radiate out from a central atom or cluster of atoms. A variety of different compounds can theoretically be attached to each of these chains, which has opened up the possibility of using dendrimers for targeted drug delivery. The problem has been that adding multiple compounds to a single dendrimer is a long and difficult process that can take months.

A simple solution to this problem, realised the Michigan researchers, is to attach single compounds to single dendrimers and then link the dendrimers together. To show the feasibility of this process, the researchers, led by James Baker, took two groups of polyamidoamine (PAMAM) dendrimers and attached a fluorescent compound to one group and folic acid to the other group. They then attached single but complementary strands of DNA, each 34 bases long, to the two dendrimer groups.

When the researchers mixed the two groups, dendrimers with complementary DNA strands bound together to form a dumb-bell-shaped complex with folic acid at one end and the fluorescent compound at the other. The researchers then showed that these complexes would be taken up by cancer cells possessing large numbers of folic acid receptors, causing the cells to fluoresce.

’With this approach,’ said Baker, ’you can target a wide variety of molecules - drugs, contrast (imaging) agents - to almost any cell’. He envisages creating a nanoparticle cluster in which one dendrimer is linked to three others, with one carrying a targeting compound, one carrying an imaging agent and one carrying a drug.

Jon Evans

Y Choi et al, Chemistry & Biology, 2005, 12, 35