Targeted nanoteranostic development of exosomes obtained from amyotrophic lateral sclerosis (ALS) patients

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease affecting both upper and lower motor neurons that can be characterized by progressive degeneration of motor neurons in the cerebral cortex, brainstem, and spinal cord. In addition, there is still no effective treatment for ALS. Current medications only slow the progression of the disease. Current approaches include intervention of antisense oligonucleotides (AONs) or CRISPR delivery systems. Disease progression is regulated by altering the intercellular communication between neurons and glial cells, also known as the pathway system. The main mediators of physiological regulation and intercellular communication are extracellular vesicles (Evs) that can transfer codes such as non-coding RNAs (ncRNAs) to recipient cells. Extracellular vesicles (EVs) are below 1000 nm and specifically exosomes are between 200 nm – 20 nm and consist of various layers of lipid monomers that occur naturally as self targeting molecules. As nanotheranostic delivery platforms for ALS diseases, EVs can be used as therapeutic and diagnostic delivery tools with various biological materials such as encapsulated nanodye, quantum dots, proteins, small RNAs, targeting biological molecules such as proteins in the lipid layer membrane structure. In particular, exosomes can easily circulate through the blood to deliver therapeutic agents and imaging agents through their self-targeting nature across the blood-brain barrier. In this study, it was aimed to develop a new theranostic-based biological nanoparticle for ALS disease. From this perspective, exosomes were obtained from the cerebrospinal fluid (CSF) of ALS patients after ultracentrifugation. Exosomes were also characterized by TEM, NTA and DSL methods. The obtained exosomes were loaded with 1,3,4 oxadiazole as a new nanotannostic agent by ultrasonication technique. At the end of the experiments, it was determined that exosomes could be successfully loaded with imaging agents and used as nanotheranostic agents. It has been proven that extracellular vesicles obtained from the CSF of ALS patients can be used as potential nanocarriers in the diagnosis and treatment of ALS, a rare disease. KEYWORDS: ALS, Exosome, Extracellular Vesicle, Theranostic, TEM, siRNA