The Application of Exosomes From Different Sources Loaded with Natural Small-Molecule Compounds in Disease

Lulu Zhang,* Changqi Shi,* Lan Yan,* Xiaomeng Zhang, Xinyu Ji, Li Li, Xiaojuan He, Yong Tan, Ning Zhao, Cheng Lu Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cheng Lu, China Academy of Chinese Medical Sciences, No. 16, Dongzhimennei South Small Street, Dongcheng District, Beijing, 100700, People’s Republic of China, Email [email protected]: Exosomes, as naturally derived nanoscale vesicles, possess inherent biological functions that make them highly efficient drug delivery vehicles. Their cellular origin dictates their bioactivity, targeting specificity, and regulatory effects, which are critical for therapeutic applications. Natural small-molecule compounds, despite their therapeutic potential, are often limited by poor solubility, instability, toxicity, and rapid clearance. Exosomes can overcome these limitations by enhancing drug stability, improving bioavailability, and enabling targeted delivery to disease sites, while also contributing therapeutic effects through their intrinsic biological properties. This review summarizes advances in the application of exosomes from diverse cellular sources for delivering natural compounds in the treatment of various diseases, and discusses the dual functional mechanisms of exosomes as both carriers and therapeutic agents, highlighting the advantages of integrating exosomes with natural small-molecule compounds. The review aims to explore novel strategies for improving the utilization of natural small-molecule compounds and to inspire new perspectives for the development of targeted nanomedicines in the future. Keywords: exosome, natural small-molecule compounds, drug delivery systems, cellular sources, disease treatment