Scientists have developed new light-sensitive chemicals that can radically improve the treatment of aggressive cancers with minimal side effects. In mouse tests, the new therapy completely eradicated metastatic breast cancer tumors.
The novel chemicals, called cyanine-carborane salts, and their role in the next-generation of cancer treatments, are described in a new article published in Angewandte Chemie, a journal of the German Chemical Society.
Photodynamic therapy, or PDT, has been used for decades to treat forms of skin and bladder cancers. It works by flooding a patient’s body with light-sensitive chemicals that accumulate in cancer cells. Shining a light on the patient activates the chemicals and kills the diseased cells.
The light causes the chemicals to generate highly reactive oxygen molecules — like tiny biochemical firecrackers — that break down cancer cells from the inside while leaving healthy cells unharmed.
It is a useful therapy with several drawbacks that limit its effectiveness, including prolonged light sensitivity, poor tissue penetration and off-target toxicity. These drawbacks can prevent complete tumor eradication and may lead to a recurrence of the cancer.
The multidisciplinary research team is composed of scientists from University of California, Riverside and Michigan State University, or MSU.
“Cyanine-carborane salts minimize these challenges, offering a safer, more precise way to destroy tumors completely while sparing healthy tissue,” said professor Sophia Lunt, MSU cancer researcher and co-principal investigator of the project.
The researchers said current FDA-approved PDT chemicals remain in the body for extended periods of time. After treatment, patients have to stay in the dark for two to three months because even low levels of light will cause them to become blistered and burned.
In contrast, the researchers found that cyanine-carborane salts flush out of the body more quickly, remaining only in the cancer cells requiring treatment.
Vincent Lavallo, UC Riverside chemistry professor and co-prinicipal investigator, is an expert on the synthesis of carboranes.
“The most interesting thing is the targeting ability of this substance we made to go right where it’s needed and stay there while the rest passes through. That way you’ll only kill the cells right where the cancer is but not harm the patient,” Lavallo said.
Lavallo worked together with Richard Lunt, MSU endowed professor of chemical engineering, to develop the cyanine-carborane salts.
Unlike conventional PDT agents, the salts exploit a natural vulnerability in cancer cells. They’re taken up by proteins called OATPs that are overexpressed in tumors. This allows for precise targeting without the need for costly additional chemicals currently used with PDT to help target the cancer cells.
Traditional PDT is also limited in its ability to treat deep-seated tumors because it works with wavelengths of light that only penetrate a few millimeters into the body. Once inside cancer cells, cyanine-carborane salts can be activated by near-infrared light that is able to move deeper into tissues. This could expand the range of cancers that could be treated.
Given their success, researchers are encouraged to continue the research and try to expand the types of cancer therapies the salts can be used with. It may be possible to alter the salts so that they can be used with energy sources other than light that penetrate even more deeply into the body.
“Our work offers a targeted, safe, and cost-effective treatment for aggressive breast cancers with limited treatment options,” said Amir Roshanzadeh, paper first author and MSU cell & molecular biology graduate student. “It also opens the door to breakthroughs in other approaches for cancer therapy and targeted drug delivery.”
The researchers thank Carl H. Schwartzkopf for supporting cancer research through his generous donation. The authors also thank the Michigan State University (MSU) Mass Spectrometry and Metabolomics Core. The Flow cytometry equipment is supported by the Equipment Grants Program, award #2022-70410-38419, from the U.S. Department of Agriculture, National Institute of Food and Agriculture. This work was supported by the National Science Foundation under CAREER Grant No. (CBET 1845006) to S.Y.L. S.Y.L. was also supported by the National Cancer Institute of the National Institutes of Health under Award Number R01CA270136 and the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number R01ES030695. R.R.L. was supported by the National Science Foundation under Grant No. (CBET 1702591). V.L. acknowledges the UC Office of the President Cancer Research Coordinating Committee award number C25CR8638 for partial support of this work.
