Engineered Exosomes–Target Designing
CD Bioparticles provides you with the customized delivery strategies, precise designs and modifications of drugs or drug-contained cargos, and advanced technical platforms can help you to solve the challenges you might meet. Our comprehensive services extend to enhancing exosome production, characterizing, purifying, and conducting potency assays.
Introduction of Target Designing
Exosomes are secreted by most cells and have a phospholipid bilayer structure. They show good compatibility between cells and some targeting ability, making them promising in precision medicine. Cells primarily internalize exosomes through endocytosis or membrane fusion. To enhance their targeting to specific tissues or organs, the surface of exosomes can be modified using biochemical or physical approaches.
Figure 1. Targeted types of engineered exosomes.
The Specific Features of Exosomes Targeting
Exosomes diversity is abundant, and their surface is rich in proteins, resulting in limited tissue specificity. Researchers primarily enhance their targeting ability by modifying the surface of exosomes. The following methods are commonly used:
- Biochemical approaches: Genetic engineering, metabolic engineering, synthetic chemistry (such as click chemistry, ring addition, affinity cleavage, carbonyl chemistry, and carbon-carbon bond addition), aptamer-receptor interactions, membrane-peptide fusion, and CD63 peptide anchoring.
- Physical approaches: Hydrophobic interactions, electrostatic interactions (using the principle of opposite charges attraction, or coating the extracellular vesicle membrane with the same charge as the target cell membrane to enhance targeting efficiency), ultrasound-guided methods, magnetic guidance, etc.
Through targeted modifications, exosomes can acquire new components and functions, significantly improving their specificity, stability, and cellular uptake. This enhances their advantages in biological delivery and therapeutic applications.
The Applications of Exosomes Targeting
Table 1. Applications of using different modification methods
| Method |
Application |
| Genetic engineering |
The construction of a pc-DNA-CTP-LAMP-2B fusion protein using a heart-specific targeting peptide (CTP, APWHLSSQYSRT), which was co-transfected into HEK293 cells using lentivirus to produce heart-targeted exosomes1. |
| Click chemistry |
Addition of ManNAz to the culture medium of parent cells allows the introduction of Azide-containing sugars into the glycan surface of secreted exosomes, achieving functionalization through bioorthogonal chemistry2. |
| Aptamer-receptor binding |
Modification of exosomes with AS1411 aptamer by conjugating it with cholesterol has been found to efficiently deliver miR-21 to leukemia cells, enhancing therapeutic efficacy3. |
| Membrane-peptide fusion |
Exosomes modified with GE11 peptide can effectively deliver let-7a miRNA to mouse xenograft breast cancer tissues expressing EGFR, significantly inhibiting tumor growth. |
| Electrostatic interactions |
Modification of exosomes by acetylating the negatively charged surface with citraconic anhydride increases the negative charge. In the presence of serum proteins, highly negatively charged exosomes are more easily taken up by macrophages. |
| Magnetic-guided |
Exosomes containing superparamagnetic iron oxide nanoparticles and tumor necrosis factor anchored by cell-penetrating peptides (CPPs) can be directed towards tumors under the influence of an external magnetic field, inhibiting tumor growth4. |
Our Target EVs Design Featured Services:
CD Bioparticles specializes in the development of drug delivery systems and customization of exosomes for efficient drug delivery. We can provide a range of services including exosomes preparation,ligand modification and activity evaluation.
Based on the methods mentioned in the literature and combined with oufr existing technological platform, we can provide you with efficient and highly active extracellular vesicle targeting modification services. Our current modification services include, but are not limited to, the biochemical methods mentioned above, such as genetic engineering, ligand-aptamer conjugation, click chemistry, or other physical methods to enhance the purity, targeting specificity, and biological activity of your extracellular vesicle products.
We also offer a range of product testing services:
- Analysis and characterization: Size analysis (NTA, TEM), biochemical analysis, (Exoview, MACSPlex…), omic analysis, dosages (proteins, DNA, RNA, Lipids…), surface-markers…
- Testing in vitro and in vivo: Cell toxicity, dose determination, pharmacokinetic assessment, and off-target effect evaluation.
Quotations and Ordering
References
- Kim H, et al.; Cardiac-specific delivery by cardiac tissue-targeting peptide-expressing exosomes. Biochem Biophys Res Commun. 2018, 499(4):803-808.
- Hakami RM, et al.; Integrating Protein Engineering and Bioorthogonal Click Conjugation for Extracellular Vesicle Modulation and Intracellular Delivery. Plos One. 2015, 10(11).
- Han Z, et al.; Improving Tumor Targeting of Exosomal Membrane-Coated Polymeric Nanoparticles by Conjugation with Aptamers. ACS Applied Bio Materials. 2020, 3(5):2666-2673.
- Zhuang M, et al.; SPION decorated exosome delivery of TNF-α to cancer cell membranes through magnetism. Nanoscale. 2020, 12(1):173-188.
Liposomes Production