Lung-Targeted Exosome Modification Service

Engineering the exosome surface membrane proteins is one of the strategies of interest to confer ligand/homing peptide and enhance targeting ability. Creative Biolabs has long accumulated the most specialized project experience and technology to enhance the combination of universal delivery ability and specific targeting of exosomes. In particular, we offer research services to facilitate exosome-targeted lung modification.

Exosome Lung-targeting Specificity

It is indispensable that the organ-specific distribution of exosomes has an impact on the effective action of exosome-delivered cargoes. With the presence of specific proteins such as CD47 on the surface, exosomes can avoid phagocytosis and receptor-mediated endocytosis by mononuclear macrophages and exhibit significantly better-circulating stability than other carriers. However, the organ-specific distribution of exosomes is accompanied by different characteristics of surface integrin expression, which raises the challenge of enrichment of exosomes toward target regions. Exosomes produced using sophisticated biomolecular engineering methods have become highly promising drug delivery vehicles. In particular, it is worth noting that their organ-targeting specificity plays a key role in the distribution and release of cargo after systemic administration. Proteomics-based studies of exosomal integrin expression patterns have identified a convergence of integrin α6β4 and integrin α6β1-targeted exosomes into the lung. This directed migration involves the recruitment and binding of integrins to raft-localized C4.4 A, MT1-MMP, allowing for a shift in adhesion and motility. Moreover, knockdown of integrin α6β4 showed reduced access to exosomes by lung cells. Similarly, through the investigation of the exosome's mediating role in the metastasis of multiple tumors and their settlement in distant organs, marker molecules targeting the lung are continuing to be discovered. These not only provide clues to the role of exosomal integrins in the propensity of tumor metastasis, but also provide new ideas for the modification and production of exosome delivery vectors for lung targeting.

Fig.1 Schematic presentation of C4.4A, α6β4, and protease cooperation. (Ngora, 2012)

Exosome Modifications Targeting the Lung at Creative Biolabs

The deeply modifiable nature of exosomes confers the possibility to manipulate their molecular composition and to confer new desired targeting properties. In the development and application of exosome delivery vectors, Creative Biolabs can not only genetically engineer the use of donor cells to obtain exosomes displaying lung-targeting peptides on their surface, but also exogenously enhance the lung-targeting ability of engineered exosomes through ligand modifications. The ligand modification is performed with the help of multiple membrane proteins as anchoring scaffolds and intermolecular linkage with the help of click chemistry. Based on this lung-targeting engineering modification strategy, it becomes possible to modify and purify and isolate exosomes for specific lung tissue/cellular targeting using molecular biotechnology and exosome isolation platforms.

Fig.2 Integrin α6β4 and integrin α6β1-mediated organotropic incorporation of sEVs. (Armacki, 2020)

Creative Biolabs has built a proven system for lung-targeted exosome customization with the support of a top-notch team of expert scientists at every step of exosome modification and analysis. We can flexibly customize and produce service solutions containing specific cargoes of engineered modified lung-targeted exosomes as clients require. Please feel free to contact us to advance your research.

References

Ngora, H.; et al. Membrane-bound and exosomal metastasis-associated C4.4A promotes migration by associating with the α(6)β(4) integrin and MT1-MMP. Neoplasia. 2012, 14(2): 95-107.
Armacki, M.; et al. Protein kinase D1, reduced in human pancreatic tumors, increases secretion of small extracellular vesicles from cancer cells that promote metastasis to lung in mice. Gastroenterology. 2020, 159(3): 1019-1035.e22.

Plant Exosome Isolation