Potential of exosomes as diagnostic biomarkers and therapeutic carriers for doxorubicin-induced cardiotoxicity

Figure 1. The biogenesis and structure of exosomes.The plasma membrane firstly invaginates into early sorting endosome (ESE) with the assistance of Golgi complex and endoplasmic reticulum. Then, ESE can generate late sorting endosome (LSE). The LSE undergoes second invagination and forms multivesicular body (MVB). MVB contains a structure called Intraluminal vesicles (ILV), which will be modified further. When MVB fuses with plasma membrane, ILVs will be released. At the time, ILV become exosomes. Exosomes are comprised of lipid bilayer and contents. The contents include nucleic acids (RNAs and DNAs), lipids and proteins. Some proteins are located on the membrane as receptor signals or receptors, some transverse the bilayer, like tetraspanin family, as hallmarks of exosomes, while some are in the exosomes, like TSG101, Alix, also function as hallmarks or play some certain roles.

Figure 2. Different sources of exosomes and contained cargos alleviate DIC. DOX induces cardiotoxicity. DOX not only kill tumor cells through circulation, it but also damages cardiomyocytes at the same time and induces senescence and various death forms of cardiac cells, such as apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis. Exosomes act as biomarkers for DIC. Exosomes are comprised of phospholipid bilayer and contents, including proteins, which are also inserted into bilayer, and nucleic acids. MiRNAs and some proteins in exosomes can be used to forecast the emergence and prognosis of DOX-induced cardiotoxicity. Exosomes function as delivery vehicles for DIC. Varieties of cells, such as dendritic cells, mesenchymal stem cells, embryonic stem cells, cardiac progenitor cells, and tumor cells can secret exosomes or transfer contained miRNAs and lncRNAs to alleviate DOX-induced apoptosis and pyroptosis, decreasing DIC.

Figure 3. Overview of the strategy for attenuating DIC based on exosomes.