Current Knowledge and Future Perspectives of Exosomes as Nanocarriers in Diagnosis and Treatment of Diseases.

Exosomes, as natural nanocarriers, characterized with low immunogenicity, non-cytotoxicity and targeted delivery capability, which have advantages over synthetic nanocarriers. Recently, exosomes have shown great potential as diagnostic markers for diseases and are also considered as a promising cell-free therapy. Engineered exosomes have significantly enhanced the efficacy and precision of delivering therapeutic agents, and are currently being extensively employed in targeted therapeutic investigations for various ailments, including oncology, inflammatory disorders, and degenerative conditions. Particularly, engineered exosomes enable therapeutic agent loading, targeted modification, evasion of MPS phagocytosis, intelligent control, and bioimaging, and have been developed as multifunctional nano-delivery platforms in recent years. The utilization of bioactive scaffolds that are loaded with exosome delivery has been shown to substantially augment retention, extend exosome release, and enhance efficacy. This approach has advanced from conventional hydrogels to nanocomposite hydrogels, nanofiber hydrogels, and 3D printing, resulting in superior physical and biological properties that effectively address the limitations of natural scaffolds. Additionally, plant-derived exosomes, which can participate in gut flora remodeling via oral administration, are considered as an ideal delivery platform for the treatment of intestinal diseases. Consequently, there is great interest in exosomes and exosomes as nanocarriers for therapeutic and diagnostic applications. This comprehensive review provides an overview of the biogenesis, composition, and isolation methods of exosomes. Additionally, it examines the pathological and diagnostic mechanisms of exosomes in various diseases, including tumors, degenerative disorders, and inflammatory conditions. Furthermore, this review highlights the significance of gut microbial-derived exosomes. Strategies and specific applications of engineered exosomes and bioactive scaffold-loaded exosome delivery are further summarized, especially some new techniques such as large-scale loading technique, macromolecular loading technique, development of multifunctional nano-delivery platforms and nano-scaffold-loaded exosome delivery. The potential benefits of using plant-derived exosomes for the treatment of gut-related diseases are also discussed. Additionally, the challenges, opportunities, and prospects of exosome-based nanocarriers for disease diagnosis and treatment are summarized from both preclinical and clinical viewpoints.