Sonodynamic Immunotherapy Proves Effective in Pancreatic Cancer Treatment
Ultrasound is a promising technique for treating cancer. Unlike laser
light, used in photodynamic cancer therapy, ultrasound waves can reach
deep into tissue—up to 12 cm—to treat deep tumors without damaging
healthy cells. A team of researchers reporting in the journal Angewandte Chemie
have now developed a sonodynamic cancer immunotherapy based on
semiconducting polymer nanoparticles joined to immunomodulators that can
be activated by ultrasound.
© Wiley-VCH, re-use with credit to 'Angewandte Chemie' and a link to the original article.
The principle behind cancer immunotherapy is using, or boosting, our
own body’s defense mechanisms in the fight against cancer. However, this
requires the tumor cells’ own defenses against our immune system’s T
cells to be overcome. Although this can be achieved using special
immunotherapeutic drugs, their action has to be limited to the cancer
cells themselves to prevent an excessive and damaging response from the
whole immune system.
In photodynamic therapy, activatable nanomedicines are transported
into cancer cells on nanocarriers which accumulate in the cells and are
then released by a reaction induced by laser light. However, laser light
cannot reach the deeper parts of the human body, meaning photodynamic
therapy is only of use for organs close to the surface and does not
provide a solution for deep, difficult-to-treat cancers such as
pancreatic cancer.
In contrast, ultrasound waves can penetrate into deeply located
tissues with fewer side effects. Here, Kanyi Pu and a team of
researchers from Nanyang Technological University in Singapore and
Donghua University in China have used ultrasound for the first time for
an effective sonodynamic treatment of orthotopic pancreatic cancer in a
mouse model.
To make the sonodynamic immunomodulation molecular system, the team
prepared nanoparticles from a specific semiconducting polymer that
responds to ultrasound. Activated by ultrasound waves, it transferred
its energy to molecular oxygen, from which singlet oxygen (a type of
reactive oxygen species) was formed in the cells to induce immunogenic
cell death and kill cancer cells. In addition, the polymer—or
“semiconducting pro-nanomodulator”—carried two specific immunomodulators
into the cells, which were released by singlet-oxygen-induced bond
breakage after ultrasound activation.
The sonodynamic treatment was exceptionally effective in mouse
models, with full recovery being achieved for mice implanted with
orthotopic pancreatic tumors. Following injection into the bloodstream,
the team used imaging methods to observe the accumulation of the
nanomodulators in tumor tissue. Treatment with ultrasound then activated
the drugs and the tumors broke down within a few days.
In other, healthy tissue, the nanomodulators that had not been
activated were harmless. “However, immune-related adverse events were
observed in the liver after the injection of the free drugs,” Pu says,
acknowledging that the prodrug development is only at an early state.
The team emphasizes that this sonodynamic method can be used to reach
much deeper parts of the body than photodynamic therapy, hugely
expanding the potential uses of immunotherapies that are activated at
tumor sites.
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About the Author
Kanyi Pu is an
Associate Professor at the School of Chemistry, Chemical Engineering and
Biotechnology (CCEB) and Lee Kong Chian School of Medicine at Nanyang
Technological University. His research focuses on the biophotonics of
organic semiconducting materials, including the development of molecular
optical imaging probes for early diagnosis, smart activatable
therapeutics for cancer therapy, and nanotransducers for
photoregulation.
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