Application of nanoparticles on diagnosis and therapy in gliomas

Abstract

Glioblastoma multiforme (GBM) is one of the most deadly diseases that affect humans, and it is characterized by high resistance to chemotherapy and radiotherapy. Its median survival is only fourteen months, and this dramatic prognosis has stilled without changes during the last two decades; consequently GBM remains as an unsolved clinical problem. Therefore, alternative diagnostic and therapeutic approaches are needed for gliomas. Nanoparticles represent an innovative tool in research and therapies in GBM due to their capacity of self-assembly, small size, increased stability, biocompatibility, tumor-specific targeting using antibodies or ligands, encapsulation and delivery of antineoplastic drugs, and increasing the contact surface between cells and nanomaterials. The active targeting of nanoparticles through conjugation with cell surface markers could enhance the efficacy of nanoparticles for delivering several agents into the tumoral area while significantly reducing toxicity in living systems. Nanoparticles can exploit some biological pathways to achieve specific delivery to cellular and intracellular targets, including transport across the blood-brain barrier, which many anticancer drugs cannot bypass. This review addresses the advancements of nanoparticles in drug delivery, imaging, diagnosis, and therapy in gliomas. The mechanisms of action, potential effects, and therapeutic results of these systems and their future applications in GBM are discussed.

Figure 1

Brain tumour. Coloured 3D diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI) scans of the brain of a 29-year-old with a low-grade glioma in the left frontal lobe. A DTI scan shows the bundles of white matter nerve fibers and is being used here for presurgical planning. The fibers transmit nerve signals between brain regions and between the brain and the spinal cord. A glioma arises from glial cells; nervous system supports cells. DTI scans show the diffusion of water along white matter fibers, allowing their orientations and the connections between brain regions to be mapped.

Figure 2

Proposed mechanism by Shubayev et al. [40] for MNP-induced macrophage recruitment into neuronal tissues. (1) Exposure to cytotoxic MNPs stimulated the formation of ROS in resident cells. (2) ROS promotes expression and release of proinflammatory cytokines, such as TNF-α. Through its two receptors (TNFR), TNF-α activates p38 and ERK mitogen-activated protein kinases pathways to (3) induce the expression of matrix metalloproteinases (MMPs) in its inactive, pro-MMP form. In addition, (4) ROS can directly promote MMP activation from proform. MMPs are the only enzymes in the body capable of degrading blood-brain and blood-nerve barriers (BBB/BNB), which (5) promotes infiltration of circulating macrophages (mΦ) into neuronal tissues. MNP size and surface chemistry determine the mechanisms and the target cells of MNP internalization, as well as extent of neurotoxicity of MNPs (the figure is taken and modified from [40]).