Nano beacon will light way for smarter drug delivery
[ UniNews Vol. 14, No. 14
8 - 22 August 2005 ] By Elaine Mulcahy
A nanoscopic molecular ‘beacon’ that will help scientists design smart gene and drug delivery systems has been developed at the University of Melbourne.
The beacon, made from single strands of DNA, is used to measure how easily DNA (for example, genes) can pass through the walls of particles designed to deliver drugs.
The innovative technique, which answers a longstanding need of scientists designing drug delivery vehicles, is the work of a team in the University’s Centre for Nanoscience and Nanotechnology (Chemical and Biomolecular Engineering).
Leading the work is Federation Fellow and Director of the Centre for Nanoscience and Nanotechnology, Professor Frank Caruso.
Professor Caruso says the past few years have seen major advances in the design of ‘molecular vehicles’ – particles that can be filled with a medicine or new genes. The vehicles then ferry their contents to the site in the body where they are needed.
“One of the major roadblocks that we have encountered in designing these molecular transport systems is how to get the vehicle contents out of their container once they reach the site where they are needed,” he says.
To achieve this effectively, the researchers need to know how big the pores in the vehicle’s membranes are and how easily the contents can pass through them. This has proved difficult.
Dr Angus Johnston, who works with Professor Caruso, says scientists designing these drug-delivery vehicles need to be able to measure the very small number of molecules which pass through the membrane.
“Normally, we could label the molecules, so we can see them as they pass through. The problem with this is that adding a label alters the size, so the ability to pass through the pore will change when the label is removed.”
Dr Johnston and Professor Caruso have developed a clever technique that overcomes this problem, allowing scientists to rapidly and accurately determine the permeability of DNA through films.
The beacons are single DNA strands which have a light-emitting molecule (a fluorophore) at one end and a quencher at the other. A fluorophore is simply a molecule that emits light and a quencher is a molecule that stops the fluorophore from emitting light.
The DNA strand self-assembles so that the two end segments pair up, forming a loop in the centre – much like the shape of a round-bottomed flask . This is the closed molecular beacon.
When the beacon is closed the fluorophore on one end of the DNA strand is close to the ‘quencher’ on the other end, which stops the fluorophore from giving off light.
To determine the permeability of the capsule, the molecular beacons are placed inside the delivery vehicle. If DNA passes through the capsule wall, the beacon opens and the fluorophore emits light – the beacon is ‘on’. If no DNA passes through the capsule, the beacon remains switched ‘off’.
The researchers used this technique with different length strands of DNA and were able to use the beacons to successfully determine whether or not the strands were able to pass through the membrane.
Professor Caruso says, “We hope to now use the technique in the design of intelligent drug-delivery systems which can transport medicine to target locations and release the contents in a controlled way.”
The research was recently published in the Journal of the American Chemical Society and highlighted in the 15 July issue of the journal Science. Funding for the research was provided by the Australian Research Council.
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