Advances in Exosome Engineering for Cardiovascular Applications

Abstract

Exosomes have emerged as favorable natural carriers of theragnostic molecules. Once considered the “disposal bags of the cells” for cellular metabolic waste, they have emerged as central players in intercellular communication. They carry bioactive-molecule cargo from donor cells to recipient cells, which respond to these signals. The cargo delivered in this process is diverse, encompassing proteins, nucleic acids, small molecules, and even gene-editing tools. Recipient cells take up cargo via one or more mechanisms, including receptor-mediated endocytosis, membrane fusion, or phagocytosis. To enhance their therapeutic efficacy, researchers have developed protocols to engineer exosomes by modifying their cargo profile and surface characteristics for site-specific delivery of bioactive molecules. Compared with their native counterparts, engineered exosomes are expected to be more therapeutically efficacious at lower doses while minimizing the undesired effects often caused by non-specific tissue uptake. While the exosomal cargo profile depends on pre- and post-loading strategies (e.g., electroporation, sonication, membrane permeabilization, or chemical transfection), multiple approaches can modify surface membrane characteristics, including genetic modulation, chemical modification, and physical and hybrid approaches. Each cargo-profile modulation and surface-modification approach has respective advantages and limitations. This narrative review summarizes exosome engineering strategies and their therapeutic use in cell-free therapy. It also examines preclinical and clinical data comparing engineered exosomes with naïve exosomes to demonstrate their superiority.