A team of researchers has created a sonodynamic cancer treatment based on semiconducting polymer nanoparticles linked to immunomodulators that can be triggered by ultrasound
Published Date – Sat 17 Jun 23 03:42pm
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New Jersey: Ultrasound has been shown to be a potential cancer treatment. A team of researchers has created a sonodynamic cancer therapy based on semiconducting polymer nanoparticles linked to immunomodulators that can be triggered by ultrasound, reports the German journal Applied Chemistry.
Cancer immunotherapy works by using or boosting our body’s defenses to fight cancer. However, this requires overcoming the tumor cells’ own defenses against our immune system’s T cells. While this is possible with specific immunotherapy drugs, their effects must be limited to the cancer cells themselves to avoid an overwhelming and damaging response from the entire immune system.
In photodynamic therapy, activatable nanomedicines are delivered to cancer cells on nanocarriers that accumulate in the cells and are then released through a laser-induced response. However, laser light cannot reach deeper parts of the body, which means that photodynamic therapy is only suitable for organs close to the surface, and cannot provide a solution for deeply refractory cancers such as pancreatic cancer.
Ultrasound, by contrast, can penetrate deep into tissue with fewer side effects. Here, Kanyi Pu and a team of researchers from Nanyang Technological University, Singapore, and Donghua University, China, used ultrasound for the first time to perform effective sonodynamic therapy of pancreatic cancer in situ in a mouse model.
To create the sonodynamic immunomodulatory molecular system, the team prepared nanoparticles from a specific semiconducting polymer that responds to ultrasound. It is activated by ultrasound, transferring its energy to molecular oxygen, thereby forming singlet oxygen (a type of reactive oxygen species) in cells to induce immunogenic cell death and kill cancer cells. In addition, the polymers — or “presemiconductor nanomodulators” — bring into cells two specific immunomodulators that are released via singlet oxygen-induced bond scission after ultrasound activation.
Sonodynamic therapy was highly effective in mouse models, and mice implanted with orthotopic pancreatic tumors recovered fully.
After infusion into the blood, the team used imaging methods to observe the accumulation of the nanomodulators in tumor tissue. The drug is then activated with ultrasound treatment, and the tumor breaks down within a few days. In otherwise healthy tissue, inactive nanomodulators are harmless. “However, after injection of free drug, immune-related adverse events were observed in the liver,” said Pu, acknowledging that prodrug development is only in its early stages. The team emphasizes that this sonodynamic approach can be used to reach deeper parts of the body than photodynamic therapy, greatly expanding the potential use of immunotherapies activated at tumor sites.
