Heart-Targeted Exosome Modification Service

With the aging population, the morbidity and mortality of cardiovascular disease (CVD) are increasing year by year. In recent years, precisely targeted therapy for CVD has become an inevitable direction for future development. Exosomes have the characteristics of low immunogenicity, low toxicity, and high biocompatibility. They can freely cross biological barriers, escape lysosome-mediated degradation, and transfer biologically active molecules from donor cells to recipient cells. However, natural unmodified exosomes quickly accumulate in the liver, spleen, kidneys, and other organs after infusion. It is difficult for exosomes to accumulate in the heart to effective therapeutic concentrations. Therefore, exosomes need to be modified with cardiac-specific targeting peptides for targeted therapy of CVD. Creative Biolabs can modify the structure of exosomes to enhance the specificity of exosomes targeting cardiac tissue, and then enhance the therapeutic effect of exosomes on CVD.

Heart-targeting Peptides for Engineered Exosomes

Recently, exosome surface display technology is a hot spot in the research field of exosome precision therapy. Using DNA recombination technology, the DNA sequence of the exogenous peptide is fused to the structural gene of the exosome surface protein, so that the exogenous targeting peptide and the surface protein are expressed together. This confers tissue targeting on exosomes. There are currently three proven cardiac tissue-targeting peptides, including ischemic myocardium-targeting peptide CSTSMLKAC (IMTP), cardiomyocyte-specific peptide (CMP), and heart homing peptide (HHP). Through plasmid construction and plasmid transfection techniques, these three polypeptides can be constructed as fusion proteins with lysosome-associated membrane protein 2 (Lamp2b) enriched on the surface of exosomes.

Fig.1 Schematic diagram demonstrates the methods for development of CDC-derived cardiomyocyte targeted exosomes and their future therapeutic potential. (Mentkowski, 2019)

Effects of Heart-targeted Exosomes

Exosomes modified by the above three cardiac targeting peptides, namely IMTP-Exos, CMP-Exos, and HHP-Exos, can target cardiac tissue more effectively in vivo. IMTP-Exos derived from bone marrow mesenchymal stem cells can be efficiently targeted to the ischemic myocardial tissue, inhibit inflammation, fibrosis, and myocardial cell apoptosis, improve angiogenesis and cardiac function, and have a good therapeutic effect on acute myocardial infarction. Cardiosphere-derived cells (CDCs)-derived CMP-Exos can inhibit cardiomyocyte apoptosis and improve cardiac function after ischemic and non-ischemic myocardial injury. CDCs-derived HHP-Exos can improve cardiac hypertrophy by blocking the STAT3/ERK1/2/AKT signaling pathway through miRNA-148a-mediated GP130 inhibition.

Fig.2 Schematic illustration of how exosomal miRNA-148a from HHP-EXO protects against pressure overload-induced cardiac hypertrophy. (Mao, 2022)

Drug delivery targeting CVD is a major challenge in the treatment of CVD. It is hopeful that, as an endogenous membrane-type carrier, exosomes can be appropriately modified to have tissue targeting, and play a great therapeutic value as a drug delivery system. Creative Biolabs can provide plasmid construction, plasmid transfection, lentiviral stable transfection, and other genetic engineering technologies to transform exosomes from the source. In addition, we can also provide customized services such as exosome extraction, identification, and functional verification. Please contact us with your needs and ideas to help you move forward with your project.

References

Mentkowski, KI.; Lang, JK. Exosomes Engineered to Express a Cardiomyocyte Binding Peptide Demonstrate Improved Cardiac Retention in Vivo. Scientific Reports. 2019. 9(1):10041.
Mao, L.; Li, YD.; et al. Heart-targeting exosomes from human cardiosphere-derived cells improve the therapeutic effect on cardiac hypertrophy. Journal of Nanobiotechnology. 2022. 20(1):435.

Plant Exosome Isolation