Organic Nanoparticles Heat Up Tumors

Nanoparticles made from conductive polymers can accumulate in tumors in mice, allowing researchers to selectively kill cancer cells with laser light (ACS Nano, DOI: 10.1021/nn301539m). When such nanomaterials absorb certain wavelengths of light, they heat up and kill surrounding cancer cells. This treatment strategy is called photothermal therapy, and researchers think it could help doctors destroy tumors without harming surrounding healthy tissue. Compared to most other nanomaterials tested for this type of therapy, the new study’s nanoparticles are less likely to persist in the body and cause long-term side effects, the researchers say.

Previous studies have focused on inorganic nanomaterials, such as gold nanostructures, carbon nanotubes, and copper sulfide nanoparticles, because they absorb near-infrared light. Light at these wavelengths can readily penetrate biological tissues to reach tumors below the skin.

Despite these methods’ effectiveness in shrinking tumors in animals, doctors worry about injecting the materials into people because they are not biodegradable, says Zhuang Liu of Soochow University, in China. The particles could remain in the body for long periods, causing toxic side effects, he says.

To avoid this issue, Liu and his coworkers wanted to develop organic light-absorbing nanoparticles, which are more likely to degrade in the human body than inorganic particles are. Researchers already use organic nanoparticles to deliver drugs or gene therapy, but those materials don’t absorb near-infrared light. Liu noticed that some conductive polymers in organic electronics strongly absorb near-infrared light. “Their potential in phototherapy may not be widely realized,” he says.

Liu and his team chose to work with a copolymer called poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate), or PEDOT:PSS. Liu found that particles of this material alone were toxic to cells. To reduce the toxicity of the particles and prevent them from aggregating under physiological conditions, the scientists had to add layers of other polymers. These additional layers allowed them to attach the polymer polyethylene glycol.

The team injected the final 100-nm-diameter nanoparticles into mice with breast cancer tumors that the scientists had inserted into their backs. The materials were remarkably stable, persisting in the mouse blood stream for more than 48 hours. Moreover, the nanoparticles accumulated mainly in the tumors. Liu says the likely reason is that tumors have leaky blood vessels, which tend to allow nanosized materials into the tumor and trap them there.

When the scientists shined near-infrared light on the mouse tumors, they watched the cancerous tissue heat up to about 51 °C, while the surrounding normal tissue’s temperature remained steady at around 30 °C. Within a day of this photothermal therapy, the tumors completely disappeared. Mice that received the therapy survived for more than 45 days after the treatment; untreated mice, mice treated with just a laser pulse, and mice who received just a nanoparticle injection survived only 16 to 18 days. When the scientists looked at the results of blood tests and tissue analyses, they saw no obvious signs of toxicity from the nanoparticles after 45 days. Liu says the team still needs to examine the particles’ long-term toxicity and biodegradation.

Jin Zhang, a chemist at the University of California, Santa Cruz, calls Liu’s work interesting and novel. However, he says that the researchers could make the nanoparticles more efficient by shrinking their size and the range of wavelengths of light they absorb.