Advances in Multicompartment Synthetic Protocells: from Design Strategies to Biomedical Application

Abstract Multicompartment synthetic protocells offer significant advantages over traditional single‐compartment systems by replicating the compartmentalized organization of natural cells. This advanced design enables effective synergy and precise control over complex biochemical reactions through modular and hierarchical structures. The construction strategies primarily encompass self‐assembly methods, microfluidic technology, and double emulsion techniques, which facilitate precise and reproducible formation of interconnected compartments separated by physical or chemical barriers. These compartmentalized architectures allow synthetic protocells to mimic natural cell functionalities, including regulated transmembrane transport, energy metabolism, and responsive behaviors triggered by environmental stimuli (e.g., pH or temperature). By segregating metabolic pathways into distinct compartments, these multicompartment synthetic protocells can significantly reduce undesirable interference between biochemical reactions, thereby enhancing reaction specificity, efficiency, and stability. This review systematically examines the recent advancements in constructing multicompartment synthetic protocells, discusses the unique characteristics empowered by multicompartment synthetic protocells, and finally highlights their potential applications, particularly emphasizing their roles in biomedical applications. Finally, current challenges and future perspectives in advancing the precision, functionality, and biomedical applications of multicompartment synthetic protocells are discussed, aiming to provide valuable insights and directions for future research.