Single‐Point Laser Irradiation Photodynamic Therapy: From Selective Plasma Damaging to Cell Death from Within the Tumor

Abstract

Photodynamic therapy (PDT) is a clinically approved anticancer treatment based on the generation of reactive oxygen species (ROS) when a photosensitizing agent (PS) is irradiated with specific light. Typically, irradiation is performed to cover the entire tumor or treatment area. However, this approach presents some disadvantages, including irradiation of the surrounding normal tissue. Therefore, this study introduces a novel phototherapeutic approach using single‐point laser irradiation. With the plasma membrane as the primary organelle target, it is demonstrated that single‐point laser irradiation induces plasma membrane damage in cancer cells using two clinically approved fluorescent markers for Glioblastoma: Protoporphyrin IX (PPIX), which localizes to the plasma membrane, and Sodium Fluorescein (NaF), which remains in the extracellular space, contacting the membrane. Single‐point laser irradiation in photodynamic therapy induces plasma membrane disruption in both cases, resulting in selective necrotic cancer cell death. Interestingly, this approach induces cell death from within the spheroids, and the cell death gradually extends to the rest of the spheroid, minimizing damage to the surrounding tissue. In conclusion, this study presents a novel approach using focused laser irradiation and clinically approved dyes to induce precise, targeted cell death within the tumor, suggesting potential for theranostic applications in tumor eradication.