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Nanoparticle lights up at the site of cancer

By Nora Schultz

12 October 2007

A new nanoparticle can multitask as a drug courier and a delivery reporter by glowing when it dumps its cargo inside tumour cells. The technique could allow doctors to see exactly which cells have successfully received a drug – if it gets approval for use in humans.

“Quantum dots” are reflective crystals about 1000th of the width of a human hair. They show much promise as medicinal tools due to their extremely bright fluorescence and the ability to carry other molecules on their surface. Until now, however, quantum dots have been continually fluorescent, regardless of which tissue they may have reached, or what job they may have done.

Using cell culture experiments, Omid Farokhzad, who is based at Brigham and Women’s Hospital, and colleagues at Harvard Medical Schoolat Harvard Medical School and his colleagues have now managed to create quantum dots that only switch this fluorescence on when they enter the target cells and delivered the drug.

Absorbed light

Key to the design are molecules called aptamers that sit on the quantum dot’s surface. Made of nucleic acids, like DNA, and looped like hairpins, aptamers can bind to specific target molecules. In this case, the ends of the aptamers recognise molecules only found on the outside of prostate cancer cells, while the stems accommodate molecules of the anti-cancer drug doxorubicin (dox).

“Normally, dox is fluorescent, but when it binds to the aptamer, the interaction between the two molecules switches the fluorescence off,” explains Farokhzad. “Dox also absorbs all the light reflected from the quantum dot, so that then doesn’t fluoresce either.”

Only when the nanoparticle has found and entered a cancer cell does it lights up again. This is because the dox is removed from the aptamers, allowing the dot to recover its fluorescence. In the lab, the quantum dots’ coloured light can be detected with a fluorescence microscope.

Safer therapy

Since the aptamers also ensure that the drug only reaches cancer cells, the side effects for other cells are much lower than if the drug were to diffuse directly through a cell’s membrane, as with conventional chemotherapy. Farokhzad believes that by varying the molecules used, his system can be adapted to target a wide range of diseases.

Alison Ross, science information officer at Cancer Research UK, says: “Using nanotechnology to target drugs to cancer cells is an exciting technique and the nanoparticles engineered in this study are smarter than ever before.” But she adds that “more research is needed to discover whether these particles could be used to benefit cancer patients in the future”.

As a next step, Farokhzad aims to test the particles in animals with prostate cancer.

Journal reference: Nano Letters, DOI: 10.1021/nl071546n

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