Ultrasound–sensitive nanoparticle aggregates target toxic doses of chemotherapy drugs to tumors while minimizing systemic toxicity.
Cells in nearly any part of the body can become cancerous and transform into tumors. Some, like skin cancer, are relatively accessible to treatment via surgery or radiation, which minimizes damage to healthy cells; others, like pancreatic cancer, are deep in the body and can only be reached by flooding the bloodstream with cell–killing chemotherapies that, ideally, shrink tumors by accumulating in their ill–formed blood and lymph vessels in higher amounts than in vessels of healthy tissues. To improve the low efficacy and toxic side effects of chemotherapies that rely on this passive accumulation, a team of researchers at the Wyss Institute at Harvard University, Boston Children’s Hospital, and Harvard Medical School has developed a new drug delivery platform that uses safe, low–energy ultrasound waves to trigger the dispersal of chemotherapy–containing sustained–release nanoparticles precisely at tumor sites, resulting in a two–fold increase in targeting efficacy and a dramatic reduction in both tumor size and drug–related toxicity in mouse models of breast cancer.

This research was recently published in the journal Biomaterials.

“We essentially have an external activation method that can localize drug delivery anywhere you want it, which is much more effective than just injecting a bunch of nanoparticles,” says co–first author Netanel Korin, PhD, former Wyss Technology Development Fellow and current Assistant Professor at the Israel Institute of Technology.

The key to this new method is the creation of nanoparticle aggregates (NPAs), which are tiny structures consisting of drug–containing nanoparticles surrounded by a supportive matrix, akin to the berries suspended in a blueberry muffin. Like chefs trying to craft the perfect pastry, the researchers experimented with a variety of nanoparticle sizes and nanoparticle–to–matrix ratios to create NPAs that are stable enough to remain intact when injected, but also finely tuned to break apart when disrupted with low–energy ultrasound waves, freeing the nanoparticles that then release their drug payloads over time, like blueberries slowly leaking their juice.

“Locking nanoparticles up in NPAs permits precise delivery of an army of nanoparticles from each single NPA directly to the tumor in response to ultrasound, and this greatly minimizes the dilution of these nanoparticles in the bloodstream,” says Anne–Laure Papa, PhD, co–first author and Postdoctoral Fellow at the Wyss Institute. “Additionally, our ultrasound–triggered NPAs displayed distribution patterns throughout the body similar to the FDA–approved PLGA polymer nanoparticles, so we expect the NPAs to be comparably safe.”

The team says additional research could further improve the performance of ultrasound–sensitive NPAs, making the platform an attractive option for safer, more effective chemotherapy delivery. It could be made even more powerful through combination with other tumor–targeting strategies such as using peptides that home to the tumor microenvironment to further guide cancer drugs to their targets. “We hope that in the future our triggered accumulation technique can be combined with such targeting strategies to produce even more potent treatment effects,” says Papa.