Nanomedicine in Clinical Photodynamic Therapy for the Treatment of Brain Tumors.

The current treatment for malignant brain tumors includes surgical resection, radiotherapy, and chemotherapy. Nevertheless, the survival rate for patients with glioblastoma multiforme (GBM) with a high grade of malignancy is less than one year. From a clinical point of view, effective treatment of GBM is limited by several challenges. First, the anatomical complexity of the brain influences the extent of resection because a fine balance must be struck between maximal removal of malignant tissue and minimal surgical risk. Second, the central nervous system has a distinct microenvironment that is protected by the blood-brain barrier, restricting systemically delivered drugs from accessing the brain. Additionally, GBM is characterized by high intra-tumor and inter-tumor heterogeneity at cellular and histological levels. This peculiarity of GBM-constituent tissues induces different responses to therapeutic agents, leading to failure of targeted therapies. Unlike surgical resection and radiotherapy, photodynamic therapy (PDT) can treat micro-invasive areas while protecting sensitive brain regions. PDT involves photoactivation of photosensitizers (PSs) that are selectively incorporated into tumor cells. Photo-irradiation activates the PS by transfer of energy, resulting in production of reactive oxygen species to induce cell death. Clinical outcomes of PDT-treated GBM can be advanced in terms of nanomedicine. This review discusses clinical PDT applications of nanomedicine for the treatment of GBM.