Photodynamic therapy technique deactivates tumors from within, using clinically approved agents

Researchers at the Madrid Institute for Advanced Studies in Nanoscience (IMDEA Nanociencia) and the National Center for Biotechnology (CNB-CSIC) have developed an innovative technique to destroy cancer cells by inducing a cascade that spreads throughout the tumor.

The strategy allows cancer cells to be selectively destroyed by irradiating a single cell with a laser. When applied to 3D tumor models, the effect propagates to adjacent cells, inducing cell death in the core of the tumor that progressively extends throughout its structure.

Photodynamic therapy is a clinically approved cancer treatment that relies on light irradiation of tumor areas where a photosensitizing agent has been previously administered. Light activation releases toxic compounds aimed at inducing the death of cancer cells. Typically, irradiation is applied to the entire tumor. Researchers now propose an innovative approach: focused laser irradiation on individual tumor cells.

The research is published in the journal Advanced Therapeutics.

Using clinically approved photosensitizing agents, the researchers demonstrated that focused laser irradiation causes selective damage to cancer cells in culture. By irradiating cells with a pinpoint light, they perforated the cell membranes, inducing the death of the targeted cell with high precision. Within less than a minute, the researchers were able to observe cell death in real time under a microscope.

The most striking aspect of this study was the observation that the effect extended to adjacent cells. To investigate this, the researchers used tumor spheroids—3D cell cultures that mimic the actual organization of cells in tumors. Cells within the spheroid were irradiated, and for the first time, it was observed that neighboring non-irradiated cells also died due to the so-called bystander effect.

The bystander effect is a phenomenon previously described in radiotherapy and also observed in photodynamic therapies, where stress signals from a damaged cell induce the death of neighboring non-irradiated cells. The researchers observed that after the pinpoint light irradiation, cell death spread throughout the entire tumor spheroid in culture within 10 minutes.

Dr. Sebastián Thompson, senior author, said, “The fact that we present this proof of concept using both markers and light already used clinically opens up an immense range of applications, since only the method of irradiating the tumor changes. This creates a much more favorable scenario for future tests in animal models. Photodynamic therapy is already in clinical use, and in the areas where it is applied—lung cancer, brain tumors, etc.—it could potentially support future applications.

“With this technique, we are inducing cell death from within the tumor spheroid, a scenario as counterintuitive as it is fascinating. For this reason, we are also theoretically investigating this phenomenon, which we have explored experimentally.”

Cristina Carrizo, the study’s first author, said, “The next steps will be to determine the limits of the bystander effect, ensure healthy cells are not damaged, and identify the tumor sizes to which this new technique could be applied to define future tests in animal models.”

In summary, the study presents a new technique within photodynamic therapy that uses clinically approved photosensitizing agents and can destroy tumor spheroids from the inside in a highly precise, cell-by-cell manner. This new concept in photodynamic therapy could be combined with other therapies or surgeries to help achieve complete cancer eradication.

The study opens new perspectives in the fight against aggressive tumors such as glioblastoma, achieving highly selective and efficient treatment. The results suggest that this single-point photodynamic therapy could become a promising complement to current oncological treatments.

Researchers at the Madrid Institute for Advanced Studies in Nanoscience (IMDEA Nanociencia) and the National Center for Biotechnology (CNB-CSIC) have developed an innovative technique to destroy cancer cells by inducing a cascade that spreads throughout the tumor.

The strategy allows cancer cells to be selectively destroyed by irradiating a single cell with a laser. When applied to 3D tumor models, the effect propagates to adjacent cells, inducing cell death in the core of the tumor that progressively extends throughout its structure.

Photodynamic therapy is a clinically approved cancer treatment that relies on light irradiation of tumor areas where a photosensitizing agent has been previously administered. Light activation releases toxic compounds aimed at inducing the death of cancer cells. Typically, irradiation is applied to the entire tumor. Researchers now propose an innovative approach: focused laser irradiation on individual tumor cells.

The research is published in the journal Advanced Therapeutics.

Using clinically approved photosensitizing agents, the researchers demonstrated that focused laser irradiation causes selective damage to cancer cells in culture. By irradiating cells with a pinpoint light, they perforated the cell membranes, inducing the death of the targeted cell with high precision. Within less than a minute, the researchers were able to observe cell death in real time under a microscope.

The most striking aspect of this study was the observation that the effect extended to adjacent cells. To investigate this, the researchers used tumor spheroids—3D cell cultures that mimic the actual organization of cells in tumors. Cells within the spheroid were irradiated, and for the first time, it was observed that neighboring non-irradiated cells also died due to the so-called bystander effect.

The bystander effect is a phenomenon previously described in radiotherapy and also observed in photodynamic therapies, where stress signals from a damaged cell induce the death of neighboring non-irradiated cells. The researchers observed that after the pinpoint light irradiation, cell death spread throughout the entire tumor spheroid in culture within 10 minutes.

Dr. Sebastián Thompson, senior author, said, “The fact that we present this proof of concept using both markers and light already used clinically opens up an immense range of applications, since only the method of irradiating the tumor changes. This creates a much more favorable scenario for future tests in animal models. Photodynamic therapy is already in clinical use, and in the areas where it is applied—lung cancer, brain tumors, etc.—it could potentially support future applications.

“With this technique, we are inducing cell death from within the tumor spheroid, a scenario as counterintuitive as it is fascinating. For this reason, we are also theoretically investigating this phenomenon, which we have explored experimentally.”

Cristina Carrizo, the study’s first author, said, “The next steps will be to determine the limits of the bystander effect, ensure healthy cells are not damaged, and identify the tumor sizes to which this new technique could be applied to define future tests in animal models.”

In summary, the study presents a new technique within photodynamic therapy that uses clinically approved photosensitizing agents and can destroy tumor spheroids from the inside in a highly precise, cell-by-cell manner. This new concept in photodynamic therapy could be combined with other therapies or surgeries to help achieve complete cancer eradication.

The study opens new perspectives in the fight against aggressive tumors such as glioblastoma, achieving highly selective and efficient treatment. The results suggest that this single-point photodynamic therapy could become a promising complement to current oncological treatments.