Exosomes, as the small particles of endosomal-derived lipid bilayers, that are a subset of extracellular vesicles (EVs) secreted by most cell types. Due to the emerging role of exosomes as intercellular messengers and their potential in disease diagnosis, the interests in exosome research have grown over the past decade. Indeed, exosomes contain proteins, lipids and RNA specific to their cellular origin that can transport cargo to nearby and distant cells. As a result, investigations into foreign goods can provide opportunities for disease detection and treatment.
Furthermore, since exosomes can be safely transported in extracellular fluids and deliver cargos to designated cells with high specificity and efficiency, they have been explored as natural drug delivery vehicles. Despite tremendous efforts in this relatively new field of research, progress has been hampered by challenges such as inefficiencies in separation methods, difficulty in characterization, and lack of specific biomarkers.
The application of exosomes is primarily the possibility of using exosomes as biomarkers for diseases and as delivery systems for therapeutic agents, which is of great importance due to their ability to cross the blood brain barrier. In specific, cancer is one of the subjects that based on exocomes biology research. The use of exosomes and their contents and surface proteins can allow early detection of cancer, which can improve prognosis and survival. Besides, exosomes also play a role in the pathogenesis of Alzheimer`s disease, and if there are proteins detected on exosomes, they can be used as indicators of Alzheimer`s disease. Another disease in which exosomes may have a major impact is diabetes. Preclinical studies have also shown that exosomes may be involved in the pathogenesis of type 2 diabetes.
Although exosomal release is a normal process, cancer cells release exosomes at higher levels and their cargo is particularly suitable for the progression of cancer. Once released from the cell, the tumor exocrine begins to circulate in the extracellular space until it reaches the target. Cancer progression is a complex process, and exosomes appear to be involved in every stage of development.
The tumor microenvironment consists of cells and non-cytokines contributed by the tumor and its surroundings. Its main components include extracellular matrix (ECM), cancer-associated fibroblasts (CAF), inflammatory immune cells, and tumor-associated vasculature. CAF plays an important role in maintaining the tumor microenvironment because different proteins are released into extracellular sites involved in various signal transduction pathways and their regulation. Almost all of these factors are released with the support of exosomes. On the other hand, immunosuppression is a major feature of the tumor microenvironment. Cancer cells show different strategies for inhibiting the immune system to clear tumor deposits. Recent studies have shown that exosomes play an important role in this process.
In addition to altering the local tumor microenvironment to promote cancer spread, tumor-derived exosomes have also been shown to promote metastasis of distant organs. Cancer cells have developed exosome-mediated strategies to influence many of the steps of metastasis. After invasion and infiltration, cancer cells can regulate the microenvironment of distant organs so that tumor cells can survive and settle before they arrive. The formation of this phenomenon can be introduced by exosomes of cancer cells.
Tumor-derived exosomes have a major impact on the immune system in cancer development. On the one hand, tumor-derived exosomes can stimulate immune responses against cancer, also known as cancer immune surveillance. On the other hand, tumor-derived exosomes can promote immunosuppression and inhibit immune surveillance, thereby invading and spreading. In fact, many tumor-derived exosomes contain molecules from parental tumor cells that directly or indirectly affect immune cell activation, development, and anti-tumor activity.
Because of their important role in disease transmission, cancer spread and metastasis, exosomes have been studied as promising therapeutic platforms. Targeting disease-derived exosomes allows researchers to control the spread and progression of certain diseases. However, when using exosomes for cancer treatment, exosomes should be avoided from cancer cells because exosomes may contain carcinogenic drivers that may contribute to cancer development.
Although scientists have made considerable efforts to use exosomes as a targeted therapeutic vehicle, future research needs to address major challenges. A major limitation in the field today is the lack of standardized techniques for isolating and purifying exosomes. Also, exosomes extracted from cell cultures change and exhibit inconsistent characteristics even when the same type of donor cells are used.
The role of exosomes in diagnosis and treatment is largely determined by cancer cell lines and animal models. Large-scale randomized clinical trials must be performed in different types of cancer for further validation and to determine diagnostic methods using exosomes as care points. The potential use of exosomes as delivery vehicles requires a more rigorous assessment. For example, how to improve the manageability, or whether it is possible to use a personalized approach to provide treatment-related exosomes.
