A review of recent advances in exosome-mediated drug delivery for regenerative therapy and immunomodulation

Abstract

Exosomes are small, nanoscale extracellular vesicles that facilitate intercellular communication through the transport of proteins, lipids, and nucleic acids. Recent advances in utilizing exosomes as promising vehicles for targeted delivery have opened up numerous opportunities for establishing next-generation exosome-based nanocarriers and therapeutics for multiple biomedical domains. Their inherent biocompatibility, low immunogenicity, nanoscale size and ability to naturally cross biological barriers make them promising alternatives to traditional synthetic drug-delivery systems such as liposomes and polymeric nanoparticles. In this review, we analyzed existing literature and provided an overview of biogenesis, molecular composition, and functional diversity of exosomes followed by a review of recent reports on their application in regenerative therapies and immunomodulation. First, we outlined the role of exosomes in angiogenesis, tissue repair, and immunomodulation. Next, we critically evaluated existing engineering solutions, including isolation techniques, cargo-loading approaches, genetic programming of donor cells, and surface functionalization strategies. Furthermore, we provided a comprehensive overview of recent research on engineered systems that enable controlled release, stability, and multifunctional design of therapeutics, such as exosome–biomaterial hybrids, synthetic exosome mimics, and exosome–nanoparticle platforms. Finally, we highlighted the significant barriers, such as vesicle heterogeneity, optimized production and standardization, and other regulatory challenges in translating exosomal therapeutics from basic research to clinical practice.