Nanomedicine in Clinical Photodynamic Therapy for the Treatment of Brain Tumors

Abstract

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.

Keywords: blood–brain barrier (BBB); chemotherapy; glioblastoma multiform (GBM); photodynamic therapy (PDT); photosensitizer (PS); radiotherapy; reactive oxygen species (ROS); surgical resection; targeted therapy; tumor microenvironment.

Figure 1

Schematic illustration of photodynamic therapy (PDT) for GBM treatment with energy diagram of the oxygen dependent response. If the photosensitizer (PS) in the ground singlet state is excited by the light wavelength, then the PS in the excited singlet state can convert to the excited triplet state via intersystem crossing. In the presence of molecular oxygen, the PS in the triplet state can undergo a Type 1 or Type 2 redox reaction, producing reactive oxygen species (ROS) that cause tumor cell necrosis, vascular occlusion, and tumor-specific host immunity.

Figure 2

Representative types of NPs classified according to nanostructure.

Figure 3

Representative reactions to modify the functional groups of PS-derivative based on (a) carboxyl, (b) hydroxyl, and (c) amine.

Figure 4

Porphyrin-containing mesoporous silica nanoparticles for PDT.

Figure 5

Graphene quantum dots (GQDs)-based nanomaterials for PDT.

Figure 6

Schematic diagram showing the mechanism of photodynamic therapy and bioimaging through long-wavelength to short-wavelength conversion of upconversion nanoparticles (UCNPs).