Currently, the main application directions of exosomes include as drug delivery carriers; Immune activation and immunosuppression of cancer; As a diagnostic and prognostic marker of cancer.
In recent years, more and more people began to pay attention to exosomes, and more and more studies on the carrier drugs, diagnosis, prognosis monitoring, immunotherapy and other directions of exosomes were conducted. At the same time, global pharmaceutical giants also entered the field.
Exosomes were first discovered in sheep reticulocytes in 1983 and were initially thought to be excess membrane proteins released during cell maturation to regulate membrane function. Exosomes are mainly derived from polyvesicles formed by the invasions of lysosomal microparticles in cells, and are released into the extracellular matrix after fusion with the membrane of the polyvesicles in vitro.
Later, scientists found through research that almost all cells secreted Extracellular Vesicles (EVs), EV has a double membrane structure, rich in inclusions (including proteins, lipids, nucleic acids, etc.), involved in inter-cell signal transmission. In EVs, there is a subgroup about 100nm in size, which is called Exosomes.
Studies have also found that exosomes can mediate the immune response, antigen presentation, cell migration, cell differentiation, tumor invasion and other aspects, and the function of exosomes depends on the cell type.
With the development of medicine, the function of exosomes has been applied in more and more disease fields. At present, exosomes have shown good effects in the treatment of tumors, cardiovascular diseases and other diseases.
Application directions of exosomes
Exosomes have great application prospects in the medical field, including disease diagnosis and treatment. In terms of diagnosis, it is especially necessary to detect exosome markers in liquid samples such as blood and body fluids so as to obtain disease-related information for experimental diagnosis, such as early diagnosis of tumor and prognostic evaluation of efficacy, etc.
In terms of treatment, it has been reported that natural and unengineered exosomes have therapeutic effects in viscera-related diseases for which they have a high uptake. The engineered exosomes are likely to increase the scope of application of exosomes, and even have the potential of clinical application.
As a drug delivery carrier
Exosomal drug loading therapy is also being explored as it can transport components to tumor cells and affect tumor progression, metastasis and drug resistance. Conversely, exosomes can also be used as drug delivery agents to build targeting properties for their use in the delivery of therapeutic agents, thus extending the current delivery methods of precision therapy.
There are many adhesion proteins on exosomes that are potential vectors in the field of gene therapy. Their nanosize and flexibility allow them to cross major biological barriers such as the blood-brain barrier (BBB).
Because exosomes are naturally occurring secretory vesicles with low toxicity, they are prevalent in the body, and thus are presumably well tolerated in the body. In addition, the inherent homing ability of exosomes hints at their potential effectiveness in drug delivery.
Secrete body outside the natural is applicable to transport protein and mRNA, micrornas, all kinds of non-coding RNA, mitochondrial DNA and genome DNA, which makes them can be used to deliver interference RNA and other therapeutic substances, existing research will be anti-inflammatory agent of curcumin, anticancer agent doxorubicin and paclitaxel loaded into the outside the body in the vesicle secretion for the treatment of the disease. Exosomal drug delivery systems can minimize immunogenicity and toxicity due to their endogenous advantages in the treatment of cancer.
In May 2021, Reyon Pharmaceuticals and MDimune entered into an agreement to jointly develop exosomal delivery based viral vaccines and mRNA therapies for rare genetic diseases.
Immune activation and immunosuppression of exosomes in cancer
Now, as I said, almost all cells secrete exosomes, it’s important what type of cells secrete exosomes, and different types of cells secrete exosomes that have different functions.
It has been found that tumor-derived exosomes carry antigens that can induce anti-tumor immunity in experimental animal models and human clinical trials. Antigen-carrying exosomes can activate immune cells to produce an anti-tumor immune response. Currently, exosomes have been used as specific stimuli for tumor immune responses.
However, tumor exosomes also exhibit a strong tumor-promoting immune response. Tumor cell derived exosomes inhibit T and NK cell activation and promote regulatory T cell function. In addition to regulating T cell cancer derived exosomes, they inhibit DC activity and promote the expansion of bone marrow derived suppressor cells (MDSC).
Therefore, exosomes play both immune activation and immunosuppression functions in cancer, which can not only block tumor growth by promoting anti-tumor immune response, but also induce tumor growth by weakening anti-tumor immunity or promoting angiogenesis. The function of activating immunity mainly depends on the antigen presentation of exosomes, while the immunosuppressive effect of exosomes mainly depends on the ligands carried by exosomes, such as proteins and mirnas, which inhibit the activity of cytotoxic T cells or promote the proliferation of immunosuppressive cells. Understanding the underlying mechanisms of these two functions could benefit targeted research or the use of exosomes to treat cancer.
As a diagnostic and prognostic marker of cancer
Exosomes are secreted from living cells and can carry a variety of DNA, RNA and protein components. They are widely present in body fluids such as blood, urine, ascites and pleural fluid of patients, and can be statively preserved under low temperature. Therefore, it is relatively easy to obtain and carry enough biological information through exosomes, which can provide early diagnosis opportunity by carrying information of early tumor markers.
Because the tests do little harm to the human body and can be detected in body fluids, they are considered as non-invasive diagnostic or minimally invasive biomarkers for diseases, with the potential to detect many pathological conditions, including cancer. Therefore, exosomes have a broad application prospect in tumor.
Currently, the potential of exosome applications has been seen in the field of exosome research. A number of exosome companies have formed a preliminary market pattern internationally, and different biotech companies are experimenting with exosomes from different sources, different engineering technologies and different payloads.
Of course, there are still many challenges, such as the diversity of biological functions of exosomes from different cell sources and the universality of large-scale production.
At the same time, the treatment is attracting more capital because it can be applied to a variety of diseases, achieving results that conventional therapies cannot. In the future, through further research and continuous innovation, it is believed that this highly potential technology will eventually play its role and benefit more patients.