Patient undergoing photodynamic therapy for basal cell carcinoma. [Image: RapidEye/Getty Images]
Researchers in the United States have identified and optimized a new type of light-sensitive molecule that could improve the treatment of aggressive cancers using photodynamic therapy (PDT) (Angew. Chem. Int. Ed., doi: 10.1002/anie.202419759). In tests with mice, they showed that PDT that uses these novel molecules can eradicate breast cancer tumors while also reducing the damage to healthy tissue.
New photosensitizers
PDT offers a targeted and noninvasive treatment modality that has previously been used for certain types of skin and bladder cancers. The technique relies on light-sensitive molecules that are injected into the patient's body, which over several days accumulate preferentially in cancer cells. When illuminated, these molecules generate highly reactive oxygen species that kill the diseased cells while leaving healthy tissue unharmed.
However, current PDT agents are typically activated by red light, which only penetrates a few millimetres into the body, and the photoactivated response is generally too weak to enable effective treatment of aggressive cancers. The light-sensitive molecules can also accumulate elsewhere in the body and remain there for up to eight weeks, which means that patients must avoid bright light for at least two months to prevent side effects such as blistering and burning.
The researchers believe that better outcomes could be achieved by designing new photosensitizers based on cyanine–carborane salts. Cyanine dyes can be tuned to absorb near-infrared light, strengthening the photoactivation further into the body, and the stable and inert carborane cluster has previously been found to reduce unwanted toxicity.
When the two compounds were injected into mice, PDT treatment eliminated primary breast tumors without any apparent side effects.
Right on target
In this work, the team optimized the composition of the carborane cluster to enable more precise and effective targeting of breast cancer cells. Initial investigations showed that two of the candidate compounds have the right molecular energy structure to enable efficient absorption of light at 850 nm. In vitro tests showed that illuminating these two molecules with near-infrared light can suppress the proliferation and migration of metastatic cancer cells. When the two compounds were injected into mice, PDT treatment eliminated primary breast tumors without any apparent side effects.
“The most interesting thing is the targeting ability of this substance to go right where it's needed and stay there while the rest passes through,” says Vincent Lavallo, University of California, Riverside. Tests indicate that the salts remain in breast tumors for up to five days, which the researchers attribute to the uptake of the molecules by a protein that is particularly abundant in cancerous tissue.
Lavallo and colleagues are now planning to progress the treatment into clinical trials, and they are keen to investigate other types of cancer that can be targeted with the cyanine–carborane salts.