Cancer

Drug-infused hydrogel coatings add firepower to nanoshell cancer treatment

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Nanoshells, shown here as tiny points of light, that accumulate in tumor vessels can be coated with drug-infused hydrogels to deliver a knockout punch
Nanoshells, shown here as tiny points of light, that accumulate in tumor vessels can be coated with drug-infused hydrogels to deliver a knockout punch
The cells in this image have turned fluorescent pink, showing that the new drug delivery system results in high cellular uptake after being irradiated by near infrared light
(A) a bare nanoparticle, (B) a nanoparticle prepared for coating and (C) a nanoparticle coated with a thin layer of drug-delivering hydrogels – the scale bar is 20 nm
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Building on previous work, researchers at Duke University have developed a new technology that wraps nanoshells in a thin film of drug-infused hydrogel, adding additional firepower to the already promising targeted cancer treatment. The hydrogel is loaded with cancer-fighting drugs and coated onto the nanoshells, which heat up when exposed to infrared light and release the chemotherapeutic drugs, delivering a one-two punch, directly to the tumour.

In 2013, Duke researchers discovered that soft-tissue tumors could be destroyed by injecting gold-covered nanoshells at the site of the tumors and heating them up by exposing them to infrared light. This photothermal treatment, which is currently undergoing clinical trials, offers a targeted approach that avoids the negative side effects associated with chemotherapy and radiation, which also destroy healthy cells, leaving surrounding flesh damaged and the immune system decimated.

The nanoshells measure around 100 nanometers wide and are tuned to absorb infrared light and quickly heat up when exposed to it, destroying the cancer cells. This is possible because the 800 nm wavelength infrared light passes harmlessly through water and tissue, allowing doctors to apply it directly to the patient’s tumour. Additionally, due to the leaky vasculature found in tumors, the nanoshells tend to accumulate there.

This targeted heat generation provided the researchers with the opportunity to deliver chemotherapeutic drugs to the site of the tumor through a hydrogel coating applied to the surface of the nanoshells. As the nanoshells heat up in response to infrared light exposure, the drug-infused hydrogel loses its water content and releases the drugs directly at the site of the tumor.

"The idea is to combine tumor-destroying heat therapy with localized drug delivery, so that you can hopefully have the most effective treatment possible," said Jennifer West, the Fitzpatrick Family University Professor of Engineering at Duke, who led the team responsible for developing the nanoshell technique in 2013. "And many chemotherapeutic drugs have been shown to be more effective in heated tissue, so there’s a potential synergy between the two approaches."

West and doctoral student Laura Strong has tested the technique in a laboratory setting, where the heating of the nanoshells took out most of the tumor cells and the drugs released from the hydrogel coating cleaned up the rest, thereby completely eradicating all the cancerous cells. Following these encouraging results, tests will be conducted in live animals, with human trials still at least a couple of years off.

And while fighting cancer is the focus of the research, West says the technology could find other applications. "The hydrogels can release drugs just above body temperature, so you could potentially look at this for other drug-delivery applications where you don’t necessarily want to destroy the tissue," she said. "You could do a milder warming and still trigger the drug release."

The team's findings are published in the journal ACS Biomaterials Science & Engineering.

Source: Duke University

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