Kidney-Targeted Exosome Modification Service

Exosomes are increasingly being investigated for their potential use for drug delivery. Based on years of experience in tissue-targeted modification and engineering of exosomes, Creative Biolabs' specialist team has the flexibility to adapt customized exosome modification protocols to customer requirements and provide research services related to exosome modifications targeting the kidney.

Overview of Exosome Targeted Delivery

Exosomes are involved in communication processes not only between cells and cells but also between cells and distant organs, which have been recognized as important carriers of substance transfer and signaling. More particularly, the similarity of their natural composition to cell membranes allows exosomes to freely cross vascular barriers, the cellular microenvironment and even the blood-brain barrier, which greatly enhances their molecular transfer function potential. There are various types of lipid and protein components on the spherical structure of the exosomes' bilayer that originate from their parent cells that play a key role in their translocation to their final settlement sites. Several studies have shown that these cell adhesion-related molecules and ligands inherently present on exosomes are able to bind to certain types of receptor organs/cells, as evidence that exosomes are able to inherit signal-targeted delivery cargoes from their parent cells. In the application of drug delivery platforms targeting the kidney, it is desired to enrich the cargo more accurately to the target organ, the kidney, with highly engineered modification of exosomes as compared to the random distribution in other organs. Based on the kidney-specific or high concentration of molecules involved in metabolic, endocrine, and other physiological processes in the kidney, the use of kidney-specific enzymes, such as L-amino acid decarboxylase, N-acetyltransferase, and phosphodiesterase, has been found to enable the localized release of chemically modified amino acid precursor drugs in the kidney. Similarly, based on the retention of folate by kidney-containing high-affinity folate-binding proteins, folate conjugates are also known to be highly kidney-selective, which provides new ideas for kidney-targeted drug studies.

Fig.1 Graphical illustration of approaches to enhance intracellular payload delivery. (Shao, 2020)

Exosome Modifications Targeting the Kidney at Creative Biolabs

The key to efficient targeted delivery of genes and drugs to the kidney lies in the suitable selection of vector types. Compared to other vectors, exosomes utilize a combination of biomolecular delivery and nanomaterials engineering to carry parent cell-derived molecules on their surface, making it easier to overcome various biological barriers and reducing safety risks. Creative Biolabs is committed to developing suitable methods to prepare exosomes for delivery to desired tissues and organs, including the appropriate selection of exosome sources, modification, and engineering of exosomes. For example, exosomes derived from renal tubular epithelial cells have a higher tropism for the kidney based on an autocrine approach compared to other tissue sources. Urinary-derived exosomes carry paracrine miRNAs that regulate renal tubular transport proteins, suggesting that urinary-derived exosomes may have renal targeting potential due to their involvement in renal metabolism. Also, the kidney has unique transport and metabolic conditions that are conducive to exosome-mediated renal targeting. As the understanding of renal structure and function improves, screening for more appropriate renal-targeting peptide modifications to exosomes allows for the targeted release of the loaded cargo. Chemical modifications via splicing reactions or lipid assembly, as well as genetically engineered modifications via fusion sequences of renal targeting peptides and scaffold proteins, are available strategies to enhance the renal targeting of exosomes without affecting the intrinsic properties.

Fig.2 Schematic of genetic modification strategies for active targeting of exosomes. (Choi, 2021)

The poor targeting of natural exosomes is overcome by adding renal targeting peptides to the bilayer membrane structure of exosomes by chemical modification or genetic modification, hence improving the delivery performance of exosomes as drug carriers to kidney tissues/cells. Creative Biolabs has built a comprehensive research platform for exosome production, cargo loading, and efficient target delivery. We have the flexibility to provide our customers with research services related to exosome modification. Please feel free to contact us for more information.

References

Shao, J.; et al. Advances in exosome-based drug delivery and tumor targeting: from tissue distribution to intracellular fate. Int J Nanomedicine. 2020, 15: 9355-9371.
Choi, H.; et al. Biodistribution of exosomes and engineering strategies for targeted delivery of therapeutic exosomes. Tissue Eng Regen Med. 2021, 18(4): 499-511.

Plant Exosome Isolation