New nanoparticle could make cancer treatment safer, more effective

The study, published in the journal Nano Letters, explores a way to make high-intensity focused ultrasound less harmful to healthy tissues.

Oregon Health & Science University was the first hospital in Oregon to offer prostate cancer treatment using a robotic-assisted high-intensity focused ultrasound device. Researchers in the OHSU Knight Cancer Institute's Cancer Early Detection Advanced Research Center, or CEDAR, wanted to improve a category of focused ultrasound known as mechanical tumor ablation.

This technique uses energy to destroy solid tumors without surgery. However, using focused ultrasound to treat solid tumors has two major challenges: it usually needs a lot of energy, which can create heat and harm healthy tissue, and even if the tumor is broken up, some cancer cells might survive and allow the cancer to come back.

"In this study, we developed a tiny particle -- about a thousand times smaller than the width of a sheet of paper -- that helps treat cancer more effectively," said Michael Henderson, B.A., the study's co-lead author.

"These nanoparticles are engineered with small bubbles on their surface. When targeted with focused ultrasound, the bubbles pop and release energy that helps destroy tumors more precisely," he said. "The particles are also coated with a special molecule called a peptide, which helps them stick to tumors and enter cancer cells more easily."

To make the therapy even more powerful, the scientists also attached a potent chemotherapy drug to the peptide on the nanoparticle's surface. Li Xiang, Ph.D., a postdoctoral scholar with CEDAR and the study's other co-lead author, describes this method as a "one-two punch."

"The ultrasound physically destroys the tumor, and the drug helps eliminate any leftover cancer cells that might cause the tumor to return," she said.

In preclinical models of human melanoma, this combination led to deeper tumor destruction and more effective drug delivery than either treatment alone.

"Our nanoparticles reduce the energy needed for ultrasound treatment by up to 100-fold," Henderson said. "This allows us to use short ultrasound pulses to disrupt tumors mechanically, without overheating surrounding tissue."

When tested in mice with human melanoma tumors, the combined treatment -- ultrasound plus the drug-loaded nanoparticles -- led to significantly better outcomes than either treatment alone. In some cases, tumors completely disappeared and improved overall survival for more than 60 days with no major side effects observed.

The new platform could eventually be used for other treatments, including infections or cardiovascular disease, where a mix of mechanical and drug therapy could be helpful.

"What began in 2018 as research into nanoparticle-assisted tumor ablation has evolved into a multifunctional platform enabled by simple mixing -- we're now excited to bring this into immunotherapy," said Adem Yildirim, Ph.D., the study's senior author and assistant professor of oncological sciences in the OHSU School of Medicine and the OHSU Knight Cancer Institute. "By combining focused ultrasound with smart drug delivery, we're seeing a promising new way to fight cancer more effectively and reduce the chance of it coming back."

Henderson said future combined treatments, in this case ultrasound and immunotherapy, could help go beyond what each therapy does on its own.