Adipose-Derived Stem Cells as Photodynamic Therapeutic Carriers for Treatment of Glioblastoma Exploiting Reactive Oxygen Species

Glioblastomas (GBM) are the most frequent and malignant human brain tumors. Although GBM incidence is low, it is almost always lethal. Standard treatment for GBM include surgery, irradiation, and temozolomide (TMZ) chemotherapy; however, these therapies are limited in efficacy due to failure of drug delivery through the blood-brain barrier, high rates of recurrence, overall resistance to therapy, and devastating neurological deterioration. There is a need for novel therapeutic intervention to prevent side effects and enhance prognostic outcome. It has been reported that reactive oxygen species (ROS) are involved in different signaling pathways to control cellular stability, where cellular redox impairment is strictly related to tumorigenesis. Different ROS can exert different biological effects, and cancer cells, due their high basal metabolic rate, are more susceptible, when compared to normal cells, to therapeutic agents targeting the cellular redox status. Therefore, anticancer drugs that destroy malignant cells driving the formation of intracellular ROS, such as photodynamic therapy (PDT), can be developed to treat GBM. PDT is based on the cascade of synergistic effects between light, photosensitizer (PS), and oxygen, which greatly favor the spatiotemporal control of the treatment. Due to the high infiltrative nature of GBM, poor biodistribution of cancer drugs are seen. However, experiments have shown that adult stem cells have an uncanny ability to home to cancer cells and tumors. Therefore, along with the means of reaching the tumor site, a noninvasive therapeutic modality with little to no side effects such as PDT can be used to potentially treat GBM.