Stimuli-Responsive Cell-Mimetic Vesicles for Advanced Pharmaceutical Systems.

Vesicles have emerged as versatile drug delivery platforms owing to their ability to co-encapsulate both hydrophilic and hydrophobic cargos, enabling combination therapies and multifunctional treatment strategies. To overcome the limitations of conventional carriers, such as insufficient accumulation at target sites and nonspecific biodistribution, extensive efforts have focused on introducing stimuli-responsive functionalities that provide spatiotemporally controlled drug release, enhanced targeting specificity, and reduced systemic toxicity. More recently, vesicle-based systems have evolved beyond passive delivery vehicles into artificial cell-like platforms capable of in situ biosynthesis, stimulus-regulated therapeutic responses, and communication with living cells. Although substantial progress has been made in vesicle engineering, existing studies have largely addressed conventional delivery systems, stimuli-responsive vesicles, and artificial cells as distinct research domains. Consequently, a comprehensive perspective describing their functional evolution toward sophisticated therapeutic systems remains lacking. This review addresses this gap by integrating recent advances across these areas to examine how vesicular platforms have progressed from drug carriers to adaptive cell-mimetic therapeutic systems. Special emphasis is placed on structural design principles that enable functional diversification, the incorporation of targeting and stimuli-responsive elements, and the emergence of artificial cell-like systems capable of localized biomolecule production and biological interaction. In addition, key challenges, including the balance between membrane stability and responsiveness, efficient molecular exchange across vesicular membranes, and the integration of multiple biological functions within a single platform, are discussed. Collectively, these advances highlight the transformation of vesicle-based systems from passive nanocarriers into programmable therapeutic entities and provide a framework for the rational design of next-generation nanomedicines.