Toward Applicability of Exosomal-ncRNA Precision vs. Nanoparticles to the Brain

Abstract

Neurodegenerative disorders (NDDs) are a serious concern as they impact brain function, and unfortunately, the progression of these diseases is irreversible. Research into the pathophysiology of NDD is quite challenging due to various limitations. Obtaining brain tissues is difficult, and there is a lack of accurate and early biomarkers. Moreover, there is a lack of personalized treatment available, and the presence of the blood–brain barrier (BBB) adds further complexity to the issue. The BBB prevents most drugs from reaching the injured brain parts, significantly reducing the effectiveness of available FDA-approved pharmacological therapy. There have been several drug delivery systems utilized to address the limitations and enhance the effectiveness of drugs targeting the brain. These systems aim to improve drug delivery to the brain, increase the efficacy of drugs in diverse brain cells, and overcome issues such as drug metabolism by the liver, resistance, and toxicity. Various forms of nanoparticles (NPs) acting as nanocarriers for the few FDA-approved drugs available for NDD treatment were first attempted, followed by more sophisticated innovative engineered NPs systems to target off-label promising drugs for NDD treatment to the brain via intranasal route nose-to-brain approach. However, this approach is costly, toxic, and still not widely used in clinical settings. Therefore, it is crucial to find novel natural NPs, hopefully from the diseased part of the body, that could be loaded with pharmacological agents and selectively target the damaged brain cells and are non-toxic and non-immunogenic to the body. Endogenous nanoscale vesicles essential for cell signaling are already present inside our body as “exosomes.” Exosomes are fascinating structures that play a vital role in cell communication. They act as a transportation system for cells to exchange proteins and genetic material in a paracrine manner. These tiny single-membraned organelles are secreted by cells and have the same morphology as a cell. They are typically within the size range of 30 to 200 nm. The ability of exosomes to transport various molecules makes them a promising tool for drug delivery and diagnostics. Exosomes’ ability to reach the central nervous system (CNS) via their inherent capacity to cross the BBB ranks it as a promising carrier tool for drug targeting, solely delivering drugs to the brain. In this book chapter, we will delve into the intriguing universe of exosomes and explore their structure, function, and possible therapeutic advantages for various NDDs.