Liver-Targeted Exosome Modification Service

An effective transport system is particularly vital for drug targeting. To improve the targeting of exosome carriers to the liver, Creative Biolabs provides research services for liver-targeted modification of natural exosomes using a technology platform that combines biomaterials science and molecular engineering. Our research team can rapidly and extensively provide cost-effective custom exosome modification services that contribute to their practical efficacy in targeting the liver.

Exosomes for Targeted Delivery

Denaturation and degradation of the carrier system in the circulation impairs the stability of drugs and molecules during delivery, being a major impediment to targeted drug release. Despite the fact that non-viral carriers such as natural exosomes improve the prolonged circulation of cargo and cause lower immunogenicity and hepatotoxicity, there is still difficulty in achieving enrichment of tissue-specific exosomal carriers after systemic administration.

Targeted therapy is mainly a drug delivery system in which carriers selectively concentrate and localize drugs to specific target areas by local administration or systemic administration under guided polarization including magnetic fields and antibodies. It involves targeting mechanisms such as biophysical targeting, biochemical targeting, bioimmune targeting and targeting precursors. Exosome targeting research is currently focused on two levels of biochemical targeting, and bioimmune targeting using membrane surface receptor/antibody specificity. With the abundant blood flow, the vascular uptake and accumulation of exosomes in the liver is high, making the liver a frequent organ of targeting in the delivery of therapeutic drugs. It is also promising to develop synthetic liver-directed drug carriers. For synthetic liver-targeted exosome carriers, displaying liver-specific ligands on their surface can achieve targeting ability to their receptors and enhance exosome enrichment in the liver.

Fig.1 Schematic illustration of exosome for in vivo delivery of Cas9 RNP for the treatment of liver disorders. (Wan, 2022)

Exosome Modifications Targeting the Liver at Creative Biolabs

With a better understanding of the targeting of hepatocyte surface receptors, key genes and regulatory targets, research on the modification and delivery mechanisms of exosomes targeting the liver has come a long way, owing to the advantages of combining targeting and steep biocompatibility. At present, exosome targeting the liver is being studied from the organ level to the cellular and molecular levels.

Creative Biolabs provides research services in various aspects, including exosome modification for targeted liver, function and mechanism, and controlled release. For example, Apolipoprotein E (ApoE) is able to bind to low-density lipoprotein (LDL) receptors on the membrane surface of hepatocytes, allowing the construction of ApoE-modified exosomes that can specifically accumulate in liver tissue. Several previous studies have shown that compared to bare exosomes, such surface-linked ApoE exosomes not only significantly improve the transfection efficiency of plasmid cargoes in hepatocytes, but their tumor suppressive effect after loading with antitumor drugs is also enhanced. Similarly, the presence of SR-B1, a specific receptor for high-density lipoprotein (HDL), was found on the hepatocyte membrane, suggesting that apo-A1, the major apolipoprotein of HDL synthesized by the liver, could serve as another potential liver-targeting peptide. It provides a new idea to confer hepatic targeting properties through the modification of apoAI-modified exosomes. In addition, it has also been discovered that exosomes expressing integrin αVβ5 can interact with hepatic vitronectin and are potential targets for studying liver metastasis. In addition to displaying exosomes on the surface with targeting peptides, choosing the appropriate source of cell types would also influence the hepatic tropism of exosomes. For example, exosomes isolated from hepatic stellate cells have a natural hepatic targeting and may serve as delivery vehicles for different hepatic drugs, facilitated by the homologous tissue targeting ability.

Fig.2 Schematic representations of the engineered Apo-A1 expression vector. (Liang, 2018)

Liver-targeted peptide-modified or hepatocyte-derived exosomes show potent liver-specific carrier delivery activity, which improve drug cycle time and stability in the pursuit of multiple liver diseases. As a leading service provider in the exosome field, Creative Biolabs is committed to providing clients with optimal modification services for targeted exosomes through surface modification and engineering edits. In addition to exosome preparation and cargo loading, we also provide research services related to exosome modification for the targeted liver to assist our clients in pursuing exosome applications. Please contact us to discuss your interest.

References

Wan, T; et al. Exosome-mediated delivery of Cas9 ribonucleoprotein complexes for tissue-specific gene therapy of liver diseases. Sci Adv. 2022, 8(37): eabp9435.
Liang, G. et al. Engineered exosome-mediated delivery of functionally active miR-26a and its enhanced suppression effect in HepG2 cells. Int J Nanomedicine. 2018, 13: 585-599.

Plant Exosome Isolation