*5.1.2. Organ tropism of EVs*

Another promising therapeutic application of EVs is through the delivery of molecules to certain organs or cells using a phenomenon known as EV tropism. There have been various attempts to use this pathway for treatment of brain disorders and cancer. For example, Alvarez-Erviti et al. [7] used EVs as part of a neuronal-specific delivery system to effect an siRNAmediated knockdown of the β-site amyloid precursor protein cleaving enzyme 1 (BACE1), an initiating enzyme required for β-amyloid peptide synthesis. A significant reduction (60%) of the BAAlzCE1, at both mRNA and protein level, was achieved in the brain cortical tissue by this delivery system, indicating its utility for the treatment of Alzheimer's disease. Zhao et al. [96] showed that systemic administration of glial cell line-derived neurotrophic factor to a Parkinson's disease (PD) mouse model, significantly ameloriated both neurodegradation and neuroinflammation through the specific transmission of the neurotrophic factor by the released EVs into the target neurons. Also Zhuang et al. [97] showed that intranasal delivery of EVs containing curcumin or the STAT3 inhibitor JS1-124 to microglial cells in mice signifi‐ cantly reduced Lipopolysaccharide (LPS)-induced brain inflammation and delayed tumour growth in the GL26 tumour model. Furthermore, Pascucci et al. [95] showed a strong antiproliferative activity of EVs delivered from mesenchymal stromal cells (MSCs) incorporated with paclitaxel, against the human pancreatic CFPAC-1 cell-line. These data suggest a more potent and specific cell target delivery system aiming to increase the anti-tumour efficiency of chemotherapeutic drugs. Skog et al. [22] demonstrated a future possibility to use EVs as a diagnostic tool for certain tumours, such as glioblastoma. These tumour cells are able to release their own EVs, which contain mRNA/miRNA and proteins into the blood stream. Various mRNA/miRNA characteristics of glioblastoma cells were detected in the blood in about onethird of the tested glioblastoma patients, suggesting its utility in diagnosis and for design of optimal treatment plans for each patient.
