Small Extracellular Vesicles-Based Drug Delivery Systems for Therapies of Gastrointestinal Tumors.

Gastrointestinal tumors pose a significant threat to human health. Small extracellular vesicles (sEVs) have emerged as a promising approach for drug delivery in the treatment of gastrointestinal tumors. sEVs exhibit intrinsic advantages over synthetic nanoparticles, including native targeting ligands, the ability to cross biological barriers via membrane fusion, and reduced immune clearance mediated by surface CD47, thereby overcoming limitations of conventional nanocarriers such as rapid opsonization and hepatic sequestration. These minute vesicles are surrounded by a stable phospholipid bilayer and can be engineered with specific targeting ligands or loaded with diverse therapeutic cargoes, thereby overcoming the limitations of conventional drug delivery systems (DDSs) and improving tumor-specific accumulation while minimizing off-target effects. In this review, we explore the recent advancements in sEV-based DDSs, with a focus on design approaches for engineered sEVs, immunotherapy-related engineered sEVs technologies, and the utilization of engineered sEVs in gastrointestinal tumors. Additionally, we discuss the current challenges and future prospects of sEV-based DDSs in clinical practice, underscore the innovative role of engineered sEVs in cancer therapy, and provide promising avenues for enhancing the treatment of gastrointestinal tumors and improving patient outcomes.