University of Coimbra researchers develop innovative molecule for cancer treatment

A team of researchers from the Department of Chemistry of the UC Faculty of Sciences and Technology Coimbra (FCTUC), in collaboration with Luzitin SA, has developed an innovative molecule that could represent a significant advance in the treatment of solid tumours using Photodynamic Therapy (PDT).

The development of effective drugs for solid tumours faces two major challenges: the selective accumulation of the drug in the tumour and its ability to penetrate tumour tissue and reach all tumour cells. The dominant approach has focused on increasingly large molecules and more complex nanoparticles which, although enhancing selectivity, compromise penetration in dense and rigid tumours.

Going against this trend, the Coimbra team adopted an innovative strategy: identifying the smallest molecular structure with ideal pharmacological properties for Photodynamic Therapy. This led to the synthesis of the molecule LUZ51, the smallest known photosensitiser capable of absorbing infrared light, which is essential for effectively penetrating human tissues.

“Photodynamic Therapy is based on the activation of a photosensitiser by red or infrared light. In the presence of oxygen, this activation triggers a cascade of chemical reactions that lead to the death of tumour cells. One of the major advantages of this therapy is its high selectivity: the drug is virtually harmless in the absence of light, allowing the tumour to be destroyed only in the illuminated area,” explains Luís Arnaut, Professor at FCTUC and researcher at the Centre for Chemistry of Coimbra (CQC).

Studies showed that LUZ51 accumulates 13 times more in tumours than in surrounding tissues, is rapidly internalised by tumour cells, and induces cell death when activated by infrared light. In animal models, Photodynamic Therapy with LUZ51 achieved complete tumour regression in mice with aggressive and relatively large tumours, while preserving healthy surrounding tissues and minimising adverse effects.

“One of the most remarkable results was observed in the treatment of a murine model of triple-negative breast cancer. Even when the primary tumour already showed signs of metastasis to the lungs, local treatment with LUZ51 led to a significant reduction — and in some cases complete elimination — of lung metastases. These findings suggest that Photodynamic Therapy with LUZ51 may activate the host’s immune system, promoting an antitumour response beyond the directly treated area,” the scientist reveals.

The molecule LUZ51 has been patented by the University of Coimbra and Luzitin SA, with patents granted in the main oncology markets. The results of the in vivo studies were recently published in the prestigious scientific journal Angewandte Chemie International Edition, in the article entitled “Seamlessly Overcoming Biological Barriers with a Small Photosensitizer to Treat Metastatic Tumours with Photodynamic Therapy”.

Despite the significant potential demonstrated, the researchers stress that LUZ51 must still be evaluated in clinical trials before it can be used in cancer patients, a process that may take around five years. Nevertheless, this discovery paves the way for a new approach to creating more selective and effective treatments that pose less of a threat to healthy tissues.