Application of Nanoparticles on Diagnosis and Therapy in Gliomas

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]).