Patient with forms of aggressive breast cancer often have access to limited treatments options that aren’t harmful to their healthy body tissue. (© Pixel-Shot – stock.adobe.com)
Photodynamic therapy shows promise in eliminating tumors in a mouse model
RIVERSIDE, Calif. — In the ongoing battle against aggressive breast cancer, light might become an unexpected ally. Scientists at Michigan State University (MSU) and the University of California, Riverside have engineered a remarkable new treatment that combines two unlikely partners, a specialized salt and near-infrared light, to target and destroy cancer cells while leaving healthy tissue unharmed. This could potentially transform how we treat one of medicine’s most challenging diseases.
Despite advances in cancer treatment over recent decades, metastatic breast cancer remains particularly challenging to treat. Once cancer spreads beyond the breast to other organs, current treatments like chemotherapy often struggle to effectively target all cancer cells without causing significant side effects. Many patients face difficult trade-offs between treatment effectiveness and quality of life. The study, published in the Angewandte Chemie International Edition, reveals this innovative approach, called photodynamic therapy (PDT). This new treatment method could offer hope to patients with metastatic breast cancer who currently face limited treatment options.
PDT isn’t an entirely new concept in cancer treatment. It’s been used since the 1970s for certain skin cancers and other conditions. However, current PDT drugs present significant challenges for patients. After treatment, they must stay in the dark for two to three months, as even low levels of light can cause blistering and burning. Many existing treatments also lack precision in targeting cancer cells versus healthy tissue.
“Cyanine-carborane salts minimize these challenges, offering a safer, more precise way to destroy tumors completely while sparing healthy tissue,” explains study investigator Professor Sophia Lunt, a cancer researcher at MSU, in a statement.
The research team developed their new treatment by combining two different types of molecules. The first is a light-sensitive dye called cyanine that can be activated by near-infrared light. The second is a special boron-rich molecule called carborane that helps stabilize the compound and prevent it from damaging healthy cells until activated. This careful engineering resulted in a more stable and selective treatment.
These specialized compounds work like tiny biochemical firecrackers inside cancer cells. When exposed to near-infrared light at a specific wavelength of 850 nanometers, they generate highly reactive oxygen molecules that break down cancer cells from the inside while leaving healthy cells untouched. This precision targeting represents a significant advance over traditional chemotherapy, which can damage both healthy and cancerous cells throughout the body.
“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,” says study investigator Vincent Lavallo, a chemistry professor at UC Riverside who specializes in creating carborane compounds.
The researchers extensively tested their compounds in laboratory studies using multiple types of breast cancer cells. They worked with aggressive breast cancer cell lines including 4T1 and 6DT1 mouse cells and human MDA-MB-231 cells. At concentrations of just 1 micromolar, the treatment reduced cancer cell survival by approximately three-fold when activated by light.
What makes this treatment particularly effective is that it works through multiple mechanisms simultaneously. Beyond directly killing cancer cells through the generation of reactive oxygen species, it also disrupts the cells’ energy production centers (mitochondria) and interferes with their ability to spread through the body.
The promising laboratory results led to testing in mice with breast tumors. Using immunocompetent FVB mice with breast tumors derived from 6DT1 cells, the researchers found that six rounds of PDT treatment dramatically shrank or eliminated tumors. Importantly, the compounds cleared quickly from healthy tissues while maintaining high levels in tumor tissue for over 100 hours, providing an ideal treatment window.
Traditional PDT is limited in its ability to reach deep-seated tumors, as it typically uses light wavelengths that only penetrate a few millimeters into body tissue. The new compounds overcome this limitation by responding to near-infrared light, which can reach deeper into tissues. This advancement could expand PDT’s use to treat a broader range of cancers.
The treatment’s precision stems from its ability to exploit a natural vulnerability in cancer cells. The compounds are specifically taken up by protein channels called organic anion-transporting polypeptides (OATPs) that are more abundant in tumor cells than healthy cells. This natural targeting mechanism eliminates the need for costly additional targeting chemicals currently used in PDT treatments.
Beyond killing cancer cells directly, the treatment showed promising effects on cancer spread. It disrupted F-actin filaments, crucial structural elements that cancer cells need for movement, and reduced the expression of proteins involved in metastasis when cancer spreads from its original site to other parts of the body. This dual action could make it particularly valuable for treating aggressive cancers that tend to spread throughout the body.
“Our work offers a targeted, safe, and cost-effective treatment for aggressive breast cancers with limited treatment options,” says lead study author Amir Roshanzadeh, a graduate student at MSU. “It also opens the door to breakthroughs in other approaches for cancer therapy and targeted drug delivery.”
Looking ahead, the research team is exploring ways to modify these compounds for use with energy sources beyond light that could penetrate even deeper into the body. While human clinical trials are still needed to confirm safety and effectiveness in patients, these early results suggest this innovative approach could offer new hope for patients with aggressive cancers who currently have limited treatment options.
Paper Summary
Methodology
The research team took a systematic approach to developing and testing their new compounds. First, they created several variations of cyanine-carborane salts in the laboratory and studied their basic properties. They then tested these compounds in three different types of breast cancer cells – two from mice (4T1 and 6DT1 cells) and one from humans (MDA-MB-231 cells). Using advanced microscopes and other analytical tools, they tracked how the compounds entered cells, where they accumulated, and what happened when exposed to near-infrared light. For the animal studies, they used special mice with functioning immune systems (immunocompetent FVB mice) and implanted breast cancer cells into their mammary tissue to create a realistic model of breast cancer. The compounds were injected into the mice’s bloodstream, and light therapy was applied every 48 hours while carefully monitoring tumor size and potential side effects.
Results
The compounds demonstrated remarkable effectiveness in both laboratory and animal testing. Without light exposure, they caused minimal damage to cells even at relatively high concentrations. When activated by 850-nanometer near-infrared light, they reduced cancer cell survival by about three-fold at just 1 micromolar concentration. In mice, tumors essentially disappeared after six rounds of treatment while untreated tumors continued growing. The compounds displayed ideal therapeutic properties, staying in tumor tissue for over 100 hours while clearing quickly from healthy tissues. They worked through multiple mechanisms, disrupting various processes that cancer cells need to survive and spread. Throughout the testing period, no significant side effects were observed in the treated mice.
Limitations
While the results show promise, several important limitations should be considered. The study was conducted primarily in mice and cell cultures, not human patients, so human trials are still needed to confirm safety and effectiveness. Testing focused specifically on breast cancer, so effectiveness against other cancer types remains unknown. Since the treatment requires light activation, it may be limited to cancers that can be reached by light. Additionally, long-term effects and potential resistance development weren’t studied due to time constraints. The mouse models, while sophisticated, cannot perfectly replicate human cancer conditions.
Discussion and Takeaways
This research represents a significant advance in photodynamic therapy by addressing several major limitations of current treatments. The novel compounds achieve more precise targeting of cancer cells through natural transport mechanisms and clear more quickly from healthy tissues, potentially reducing side effects. They can generate multiple types of cancer-killing molecules and interfere with both cancer cell survival and spread. The approach may also offer cost advantages by eliminating the need for additional targeting agents. These findings suggest this approach could lead to more effective and better-tolerated treatments for aggressive cancers.
Funding and Disclosures
The research received support from multiple sources including the National Science Foundation, National Cancer Institute, National Institute of Environmental Health Sciences, and Equipment Grants Program from the U.S. Department of Agriculture. Additional funding came from Michigan State University and the University of California. The authors declared no conflicts of interest in conducting or reporting this research.
Publication Information
The study was published in Angewandte Chemie International Edition in 2025 under the title “Next-Generation Photosensitizers: Cyanine-Carborane Salts for Superior Photodynamic Therapy of Metastatic Cancer.” The research was conducted colleagues at Michigan State University and the University of California Riverside.
