**2. Overview and biogenesis of extracellular vesicles**

As membranous vesicles, many cell types in the human body release EVs and cancer cells actively secrete EVs even during the early phase of the disease. Another interesting characteristic of EVs is that its contents are protected from degradative enzymes in body fluids [13]. Based on various characteristics, ranging from size, biogenesis, content, cell of origin, morphology, EV are categorized into four main classes: endosomal-derived small exosomes (Exo) (30–150 nm), plasma membranederived middle-sized microvesicles (MV) (100–1000 nm), and large oncosomes (LO) (1000–10,000 nm), as well as apoptotic bodies (500–4000 nm) that are released from dying cells [14].

## **2.1 Exosomes**

Typically, exosomes are about 30–150 nm in diameter and are generated via an endosomal route [15–17]. Exosomes are generated through the endosomal network. This is a compartment, which is membranous in nature and aids in the sorting and direction of intraluminal vesicles such as cell surface membranes and lysosomes to their specific destinations. It is known that exosomal vesicles are formed during an inward budding of early endosomal limiting membrane, which develops into multivesicular bodies in the process [17–19]. When late endosomal membranes invaginate, intraluminal vesicles (ILVs) are formed within the larger multivesicular bodies [20]. It is during this process that the molecules carried by exosomes including proteins, lipids and nucleic acids are incorporated into the invaginating membrane whiles the components of the cytosol are engulfed by the ILVs [21]. They are liberated into the surrounding body fluids when the multivesicular bodies fuse with plasma membrane. The general function of these early endosomes and multivesicular bodies are endocytic and transportation of the cell's material. These include storage, recycling, transport, protein sorting and release of these materials [16].
