Dendrimers for drug delivery
that could improve the treatment of cancer, avoid side effects and
even report back on the success of treatment.
The team, from the University of Michigan's Centre for Biologic Nanotechnology, have used lab-made molecules called dendrimers as the backbones of their delivery system, according to physics doctoral student Almut Mecke. She presented her work at a meeting of the American Physical Society in Montreal, Canada, 23 March.
Mecke's part of the project focuses on finding out how to get dendrimers into cancer cells without disrupting healthy cells. Previous work has shown that high concentrations of dendrimers are toxic - even without their cancer drug cargo - although the mechanism behind this has not been established.
She used an atomic force microscope to generate three-dimensional images of the interactions between dendrimers and membranes similar to those that surround living cells. What she saw was that "certain kinds of dendrimers disrupt membranes by literally punching holes in them."
"Dendrimers usually have a charge, and so do cell membranes," Mecke noted. "It's the interaction between those charges that causes dendrimers to bind to cell membranes and disrupt them. What our group found is that if you modify the surface of the dendrimers chemically, they become uncharged" and leave membranes intact.
Other research at the centre showed that charged dendrimers are just as likely to enter healthy cells as cancer cells but that uncharged dendrimers do not invade cells at all unless they have cancer-detecting targeting agents attached.
"We can show that, with the targeting molecule attached, an uncharged dendrimer goes into cancer cells - and only cancer cells - and that's what we want," said Mecke.
Early results of studies with mice show that the nanoparticle drugs do treat cancer effectively with fewer side effects than conventional chemotherapy drugs. The team now want to add more functions to their dendrimer-drug devices, such as biosensors that can report on cancer cell death, indicating how successful a particular treatment has been.
