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Biomedical engineers at Duke University have developed a method to more precisely heat up gold nanoparticles to target and destroy cancerous tumors. Using imaging methods that combine light and sound to peer deeper into tissue, the team was better able to track and heat up nanoparticles to destroy a bladder cancer tumor in an animal model.
The research appeared August 13 in the journal Science Advances.
In the quest for non-invasive cancer therapies, light-based treatments like nanoparticle-mediated photothermal therapy (PTT) have emerged as promising candidates. During these therapies, nanoparticles, often shaped like rods or tiny stars, are injected into the body and travel via the circulatory system before accumulating in cancerous tumors. Once enough nanoparticles saturate the tumor, lasers are used to heat up the particles, which can then destroy the surrounding cancerous cells. Nanoparticle-based PTT has even recently been used to successfully treat prostate cancer in humans, and additional clinical trials are ongoing.
Although PTT helps minimize any off-target damage that often accompanies light-based therapies, the approach isn’t without its problems. Often when the nanoparticles are heated, they change their shape, morphing from a star into a sphere, which in turn limits their efficacy. Researchers have also lacked the imaging tools capable of accurately tracking the temperature and location of the particles in deep tissue.
“When we wanted to take a temperature measurement, we needed to use an invasive thermal probe, which wasn’t much more sophisticated than a regular cooking thermometer,” said Aidan Canning, a PhD student the lab of Tuan Vo-Dinh, the R. Eugene and Susie E. Goodson Distinguished Professor of Biomedical Engineering at Duke. “These probes could also absorb the laser light, which skewed the deep tissue readings.”
But Canning found a solution to these long-standing problems just a few labs away at Duke.
Tri Vu was a PhD student in the lab of Junjie Yao, the Jeffrey N. Vinik Associate Professor of Biomedical Engineering, where he was working on photoacoustic tomography, an imaging technique that involves shooting a laser into tissue and measuring the resulting ultrasonic wave to create colorful images. At the time, Vu had been creating a full-ring array for small animal imaging that he dubbed photoacoustic computed tomography (PACT).
“It looks like a miniature MRI machine,” explained Vu, now a research assistant professor at University of Oklahoma. “But when an animal like a mouse is placed in the system, we can capture deep tissue imaging through the animal’s whole body.”
Canning had heard about Vu’s technology and was curious about how it would pair with his nanostars. The feeling was mutual for Vu. In initial experiments, the team found that Vu’s imaging system could easily track the accumulation of Canning’s nanostars in the targeted tumors and tissues throughout the animals. They also discovered that the thermal sensitivity of photoacoustic imaging enabled the team to more precisely measure the temperature of the nanostars and surrounding tissue.
Canning and Vu tested the efficacy of their system in a mouse model for bladder cancer using an updated version of the gold nanostars. Canning’s new design encases each nanostar within a hollow gold shell that stabilizes the star’s branches as they heat, preventing them from melting into spheres. When coupled with Vu’s PACT system, the team was easily able to detect and image the nanostars and monitor the progress of the photothermal treatment. By more precisely monitoring the temperature, the team was able to observe the ideal temperature dosage needed to activate the nanostars and destroy cells.
The combination of these technologies resulted in a 100 percent survival rate in their bladder cancer models, and there was no observed treatment-related toxicity or damage to the surface tissue.
“The integration of these technologies was a significant step towards addressing field-wide challenges and pursuing more personalized treatment,” said Canning.
The duo already plans to continue their work by investigating how these tools perform in larger animal models. They also hope to explore how they can use their tools to illustrate how PTT can be used in combination with other treatment methods such as immunotherapy to optimize anti-cancer immune responses.
“This work opens up a lot of opportunities to explore new ways to advance and improve photothermal therapies using photoacoustic imaging,” said Vu. “Aidan and I are both grateful that our labs and Duke BME helped foster an environment where that collaboration was possible.”
Reference: Canning AJ, Vu T, Menozzi L, et al. Advancing precision photothermal therapy by integrating armored gold nanostars with real-time photoacoustic thermometry and imaging. Sci Adv. 2025;11(33):eadx6350. doi: 10.1126/sciadv.adx6350
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