Small extracellular vesicles (sEVs): discovery, functions, applications, detection methods and various engineered forms.

INTRODUCTION: Extracellular vesicles (EVs) are cell-created delivery systems of proteins, lipids, or nucleic acids, and means of extracellular communication. Though sEVs were initially considered to be the waste disposal mechanism, today they are at the forefront of research with different biological and pathological functions. Such EVs play a key role in the immunoregulation, CNS development, nervous system physiology, mammary gland development, induction of immunosuppression in pregnancy, the developmental signaling pathways, regeneration of different tissues, inflammation, angiogenesis, coagulation, apoptosis, stem cell differentiation, and extracellular matrix turnover. AREAS COVERED: SEVs contribute to the pathogenesis of different cancers and the progression of various neurodegenerative diseases, infections, as well as metabolic and cardiovascular diseases. Expert Opinion: There is no exact classification for EVs; however, according to size, density, morphological features, content, and biogenesis, they can be categorized into three major classes: microvesicles (ectosomes or microparticles), apoptotic bodies, and sEVs. SEVs, as an important class of EVs, have a crucial role in distinct biological functions. Moreover, shedding light on different structural and molecular aspects of sEV has led to their application in various therapeutic, diagnostic, and drug delivery fields. In this review, we have endeavored to elaborate on different aspects of EVs, especially sEVs.