Exosomes—Nanocarriers for Better Medicine

Dear Colleagues,

Exosomes are membrane-derived nano-vesicles of about 30–200 nm in size released by all types of cells. They were originally thought to function only as cellular garbage disposals. Our increasing knowledge of why cells release exosomes and their role in intercellular communication has revealed their very complex and sophisticated contributions to health and disease.

The exosomes originate with the inward budding of the plasma membrane to form early endosomes. Then, the early endosomes mature into late endosomes or multivesicular bodies (MVBs). During this process, the endosomal membrane invaginates and buds into surrounding lumina with cytoplasmic content to generate intraluminal vesicles (ILVs). After a variable amount of time in the cytosol, exocytic fusion occurs with plasma membrane in some MVBs, followed by release of their ILVs, defined and known as exosomes, to the extracellular milieu.

Exosomes are a natural nanoparticle bio-vehicle that are stable, membrane-permeable, and can even pass through the BBB.

Exosomes play a significant and diverse role in the intercellular communication that is essential for the development and function of multicellular organisms. Once released, exosomes can be taken up by cells in an autocrine, paracrine, or endocrine manner. They modulate local and distant communication with other cells. This is how cells in our body “talk” to each other and exchange information.

On one hand, exosomes play a role in disease and tumor pathogenesis; on the other hand, they can be used in personalized medicine for drug delivery and early detection of diseases, cancer in particular.

Several routes by which exosomes are taken up by target cells have been described and include endocytosis, direct membrane fusion, and receptor–ligand interaction. Exosomes are characterized by their size and content. They carry many cargos, e.g., proteins, lipids, nucleic acids, and metabolites, that vary between different cells. Their heterogeneity is derived from the original cell’s membrane and cargo they carry and deliver.

Recently, several characterization and validation methods have been developed for both research and clinical purposes to analyze exosome purity and to quantify exosomal cargo. These methods include microscopic methods (TEM, SEM, atomic force microscopy (AFM)), nanoparticle tracking analysis (NTA), dynamic light scattering (DLS), resistive pulse sensing, enzyme-linked immunosorbent assay (ELISA), flow cytometry, and microfluidics and electrochemical biosensors.  

Exosomes may play a role in metabolic diseases formation. They play a role in obesity and insulin resistance on one hand, and in cachexia and metabolic paraneoplastic syndromes on the other hand. Exosomes are suggested to be involved in spreading neurodegenerative diseases, including Parkinson’s disease (PD) and Alzheimer disease (AD). In oncology, it is suggested, that cancer cells release exosomes to modify the microenvironment making it preferential for cancer cells to survive and metastases.

There are many exciting medical applications for Exosomes:

1. Diagnosis. Exosomes represent an ideal noninvasive biomarker as they can be detected in bodily fluids.
2. Therapeutic agent. Exosomes can recognize specific cells, so they can deliver therapeutic cargos with better efficacy and less toxicity than other bio-vehicles (e.g., liposomes).
3. Injected exosomes are efficient at entering other cells and can deliver a functional cargo with minimal immune clearance.
4. Some researchers are exploring the use of exosomes in enhancing antitumor immune responses.

Over the next few years, several important developments are expected to strengthen and expand the current knowledge of exosomes. Exosomes should not be regarded as a future topic in medicine but rather the current one.

Prof. Dr. Nadir Arber
Dr. Shiran Shapira
Guest Editors

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• extracellular vesicles
• MVBs
• nanocarriers
• early detection
• therapy