CD47-Expressed Exosome Modification Service

Modification of the exosome surface with the transmembrane protein CD47 enables it to interact with the receptor SIRPα (signal regulatory protein α) present on macrophages, so as to protect exosomes from phagocytosis and increase accumulation in tumor tissues. Creative Biolabs offers customized CD47-expressed exosome modification and manufacturing services to help improve the targeted delivery performance of exosomes.

Anti-phagocytosis Effect of CD47-SIRPα Mutual Recognition

CD47 is a widely expressed transmembrane glycoprotein, also known as integrin-associated protein, which is a typical representative of the "marker of self" among all cellular expression targets. The protein has an immunoglobulin variable N-terminal domain, five transmembrane domains, and a short C-terminal intracellular tail with four variable splice isoforms, resulting in four isoforms. CD47 isoform 2 is expressed mainly in hematopoietic cells, vascular endothelial cells, and epithelial cells, isoform 1 is expressed in keratin-forming cells, and isoforms 3 and 4 are expressed in neuronal cells, intestinal mucosal cells, and testicular cells.

CD47 protects host cells by escaping phagocytosis. Host cell-expressed CD47 binds to SIRPα as well as SIRPγ expressed by immune cells and interacts with integrins, causing phosphorylation of ITIM tyrosines. The phosphorylated ITIM then recruits and activates the tyrosine phosphodiesterase SHP-1/2 protein, which inhibits the aggregation of myosin at the subsynaptic assembly site of macrophages as a "don't eat me" signal. In this way, the phagocytosis of macrophages is inhibited and cells are protected from being eliminated by the immune system. CD47 is a key regulator of tissue homeostasis, and its absence leads to phagocytosis of old or damaged cells. Therefore, CD47 can be used to modify exosomal surface membrane proteins, thus conferring anti-phagocytosis properties to exosomes.

Modification and Application of CD47-expressed Exosomes

Exosomes are distinguished from other nanoparticle carriers by the presence of transmembrane proteins on their surface that enhances endocytosis and delivery of contents. The engineered modification of CD47-expressing exosomes blocked the formation of macrophage pseudopods and evaded phagocytosis. Combined with multiple interventional treatments as well, it has been applied in several studies of tumor treatment, which exerted the strong permeability and excellent retention effect of exosomes in tumors. For example, one study constructed a CD47 overexpression plasmid and effectively loaded CD47 onto exosomes of donor cells by gene transfection. Such CD47 surface-functionalized exosomes exhibited lower toxicity to the liver and kidney compared to control exosomes. Similarly, exosomes secreted by normal fibroblast-like mesenchymal cells were genetically engineered to modify CD47 to enhance the specificity of the loaded shRNA for targeting KRAS in pancreatic cancer. In addition, the exosome surface modification of CD47 is compatible with the modification or loading of other functional cargoes. There are studies to develop engineered sEVs with high CD47 expression and c(RGDyC) modification for the delivery of epigenetically regulated proteins targeting gastric cancer. This versatile exosome platform exhibits great potential for intervention in various types of malignancies and is a specific and low-toxicity strategy.

Fig.1 Exos^CD47 escape from MPS in vivo. (Du, 2021)

Most injected nanomaterials are phagocytosed by MPS, preventing them from being delivered to the desired region, with various problems such as poor biodistribution and cationic ligand toxicity in applications. Creative Biolabs has established a comprehensive research platform including exosome engineering modification, cargo loading, labeling, and tracking, enabling it to provide CD47-expressed exosome modification and related probing services. Please contact us with your interest.

Reference

Du, J.; et al. Designer exosomes for targeted and efficient ferroptosis induction in cancer via chemo-photodynamic therapy. Theranostics. 2021, 11(17): 8185-8196.

Plant Exosome Isolation