Phototherapy Treats Metastatic Disease Using Light-Sensitive Drugs

A new study could expand the use of phototherapy for treating metastatic disease. Researchers have demonstrated the treatment of disseminated cancer by delivering photoactivatable drugs within tissues and inside cells in vivo.

According to the study, which was done at Washington University School of Medicine, light emitted as part of traditional cancer-imaging techniques to locate metastatic tumors also can trigger light-sensitive drugs. The study shows that when photosensitive drugs are packaged into nanoparticles that target irradiated cancer cells, the light-sensitive drug can produce free radicals that kill the tumor cells. Researchers demonstrated the technique in mice with multiple myeloma and aggressive metastatic breast cancer.

A new anti-cancer strategy wields light as a precision weapon. Unlike traditional light therapy — which is limited to the skin and areas accessible with an endoscope — this technique can target and attack cancer cells that have spread deep inside the body, according to researchers led by Samuel Achilefu, Ph.D. Courtesy of Washington University.

The technique harnesses the chemotherapy drug titanocene. As a chemotherapy agent alone, titanocene has not worked well in clinical trials. But when exposed to the radiation emitted by visible light, titanocene produces reactive particles that are toxic to cells, even at low doses. An orthogonal-targeting strategy and a contact-facilitated nanomicelle technology enabled highly selective delivery and colocalization of titanocene and radiolabeled fluorodeoxyglucose (FDG).

Researchers packaged low doses of titanocene inside nanoparticles targeted to proteins that sit on the surface of cancer cells. When the nanoparticles made contact with the cancer cells, their membranes fused, releasing the titanocene into the cancer cells.

FDG, a cancer imaging agent that is also a sugar, was then delivered to the cancer cells. The energy-hungry cancer cells consumed the FDG at high rates, causing tumors to glow during a PET scan. The glow triggered the titanocene, releasing free radicals and killing the cells.

Mice with multiple myeloma were treated using this strategy once a week for four weeks. In the weeks following, the treated mice had significantly smaller tumors and survived longer than the control mice. The mice with breast cancer also showed an anti-tumor effect when treated using this strategy, though less pronounced than in those with multiple myeloma. The researchers also found that certain types of multiple myeloma were resistant to this technique. They determined that the resistant multiple myeloma cells lacked the surface proteins used to target the titanocene-loaded nanoparticles.

“This is an opportunity to learn because it’s similar to what is seen in patients — some of the cells become dormant but don’t die after treatment,” professor Samuel Achilefu said. “When we looked closer at the cells that were resistant to our phototherapy, we saw that the surface protein we are targeting was not there. So next, we want to find out if we can pinpoint another surface protein to target and kill these resistant cells along with the myeloma cells that did respond to the original therapy, which could lead to complete remission.”

Unlike traditional light therapy, this technique can target and attack cancer cells that have spread deep inside the body.

“Cancer that has spread remains the major reason patients die,” said Achilefu. “Our study shows that this phototherapeutic technology is particularly suited to attacking small tumors that spread to different parts of the body, including deep in the bone marrow.”

Achilefu envisions doctors being able to one day use this type of technology to prevent cancer from recurring.

“We are interested in exploring whether this is something a patient in remission could take once a year for prevention,” he said. “The toxicity appears to be low, so we imagine an outpatient procedure that could involve zapping any cancerous cells, making cancer a chronic condition that could be controlled long-term.”

The research was published in Nature Communications (doi:10.1038/s41467-017-02758-9).