Artificial "zombie" cells: An emerging platform for targeted drug delivery and disease treatment

Living cell therapy represents a promising strategy for targeted drug delivery and personalized medicine. However, its clinical translation is limited by complex isolation procedures, stringent storage conditions, and inherent risks of pathogenicity. Derived from this approach, cell membrane-coated carrier technology also faces challenges related to scalability and intricate multistep fabrication. To overcome these limitations, artificial "zombie" cells (AZCs) therapy has emerged as an innovative alternative. This therapy employs simple methods, such as cryogenic shock, intracellular hydrogelation, or cryo-siliconization, to inactivate cells. This process eliminates potential pathogenicity while preserving membrane integrity and drug-loading functionality. Based on the intact cellular structure or engineering approaches, these "zombie" cells gain drug-loading capacity, targeting ability, and therapeutic potential. Compared to traditional therapies, AZCs therapy requires simplified processing and offers enhanced stability and improved safety, demonstrating promising efficacy in treating various cancerous and inflammatory diseases. Current AZCs exhibit diverse types, heterogeneous preparation methods and varied therapeutic mechanisms, highlighting the lack of systematic consolidation in this field. Therefore, this review comprehensively analyzes their preparation technologies, functionalization strategies, mechanisms of action, and disease applications of AZCs, to evaluate current research progress and clinical potential, offering insights to advance preclinical-to-clinical translation.