Exosome-based Delivery System Development

The existence of the blood-brain barrier prevents drugs from entering the brain, making it difficult to treat brain diseases, including brain tumors. However, in recent years, exosomes have shown great potential as drug delivery vehicles in the study of brain diseases, especially brain tumors. Experimental results in animal models have shown that modified drug-carrying exosomes can cross the blood-brain barrier.

Figure 1. The application of exosomes in the treatment of brain diseases. (Ye, S. J., et al., 2020)

We offer a strategy for the development of exosome-based drug delivery systems for brain tumors

Exosomes have the natural ability to bypass the blood-brain barrier, which can improve the efficiency of drug delivery in the brain. Its high targeting ability also helps to improve drug efficacy and reduce its toxic side effects. Although exosomes have a certain natural targeting ability, their targeting is not strong enough to meet the requirements of brain tumor therapy. To improve the targeting ability of exosomes, Alfa Cytology has made various modifications to the surface of exosomes.

We have inserted the gene encoding the targeting protein into the donor cell to make the donor cell secrete the protein in exosomes. The modification of the exosome surface has been achieved using genetic engineering. In addition, we are also trying a simpler, effective, and fast way to prepare targeted exosomes by using copper-free click chemistry and non-covalent methods to bind functional ligands to the exosome surface. This can be used for exosomes pre-isolated from culture media or body fluids, and can also be used to simultaneously conjugate multiple ligands with different properties.

The advantages of developing exosomes as drug delivery vehicles for brain tumors

• Easier storage and higher safety. They do not cause immune rejection by deposition in the brain. In addition, we offer the possibility of isolating exosomes from patients' body fluids, which can be transferred back to the same patient after modification, greatly reducing the possibility of immune reactions in the clinic.
• The stability of the drug can be improved. It can protect nucleic acid from hydrolysis by nucleases during transport. At the same time, our modified exosomes can directly enter the cytosol to avoid metabolic elimination, thus prolonging the circulation time of the drug in the body.
• The exosomes are nanoscale molecules and carry cell surface material. It has a strong ability to penetrate various biological barriers.
• Donor cell-based targeting ability. Our modified brain tumor cell-derived exosomes carry brain tumor-specific antigens, proteins, and RNAs, which can play an anti-tumor immune role.

Alfa Cytology can customize exosomes with different targeting classes and capabilities by genetically engineering exosome-derived cells or by directly modifying exosomes. In addition, we are developing exosomes as potential therapeutic targets for brain tumors, allowing drugs to be used as future anti-brain tumor treatments by inhibiting the production of exosomes from brain tumor cells. If you have a specific need for brain tumor targeted modifier molecules, please contact us for the latest proposal.

Reference

1. Ye, S. J., et al. (2020). "Research progress of exosomes as drug delivery systems in the treatment of brain diseases." Acta Pharmaceutica Sinica, 55(7): 1540-1548.