Can Extracellular Vesicles as Drug Delivery Systems Be a Game Changer in Cardiac Disease?

Abstract

Cardiac diseases such as myocardial infarction and heart failure have been the leading cause of death worldwide for more than 20 years, and new treatments continue to be investigated. Heart transplantation, a curative treatment for severe cardiac dysfunction, is available to only a small number of patients due to the rarity of donors and high costs. Cardiac regenerative medicine using embryonic stem cells and induced pluripotent stem cells is expected to be a new alternative to heart transplantation, but it has problems such as induction of immune response, tumor formation, and low survival rate of transplanted cells. On the other hand, there has been a focus on cell-free therapy using extracellular vesicles (EVs) due to their high biocompatibility and target specificity. Exosomes, one type of EV, play a role in the molecular transport system in vivo and can be considered a drug delivery system (DDS) innate to all living things. Exosomes contain nucleic acids and proteins, which are transported from secretory cells to recipient cells. Molecules in exosomes are encapsulated in a lipid bilayer, which allows them to exist stably in body fluids without being affected by nuclease degradation enzymes. Therefore, the therapeutic use of exosomes as DDSs has been widely explored and is being used in clinical trials and other clinical settings. This review summarizes the current topics of EVs as DDSs in cardiac disease.

Exosomes derived from MSC as drug system in osteoarthritis therapy

“…Unlike cell therapy, EVs face fewer ethical restrictions and a lower risk of immune rejection and malignancy. Meanwhile, compared with MSCs, which require strict conditions to maintain their vitality, MSC-Exos can be easily maintained and stored ( Okamura et al, 2023 ). Currently, many researchers utilize artificially derived extracellular vesicles, such as lipid nanoparticles and liposomes, for their studies because they allow for precise engineering design and offer higher reproducibility.…”

Research Advances of Engineered Exosomes as Drug Delivery Carrier

“…Engineered exosomes with functionalized ligands modified on the membrane surface or nanomaterials encapsulated inside have been applied for disease treatment . Compared with some other delivery systems, engineered exosomes have excellent endogenous and biocompatibility, and can exist stably in body fluids and are not readily cleared by phagocytes, which can provide better protection for drugs. , Currently, engineered exosomes have been widely applied as targeted drug carriers, such as in cancer, cardiovascular diseases, brain diseases and ulcerative colitis. − (Figure ).…”

Extracellular Microvesicles Modified with Arginine-Rich Peptides for Active Macropinocytosis Induction and Delivery of Therapeutic Molecules

“…Inward budding of the intracellular multivesicular body (MVB) membrane with cytosolic molecule encapsulation leads to the generation of exosomes. The fusion of the MVB and plasma membranes causes exosome secretion to external cells. − In contrast, MVs are generated by budding of the plasma membrane with phosphatidylserine and phosphatidylethanolamine externalization. ,, Plasma membrane composition is affected by enhanced calcium concentrations and calpain activation, causing direct outward membrane budding and MV release . Calpains and actin–myosin-based contraction mediated by ARF-1/RhoA/ROCK/MLCK cascade pathways cause cytoskeleton weakening, which facilitates membrane blebbing and MV shedding .…”