Advances of Cell Membrane-Coated Nanotechnology and Membrane Vesicles in Intestinal Targeted Drug Delivery Systems

Although nanomedicine has enabled significant advances in drug delivery, the clinical translation of conventional synthetic nanocarriers is limited by immune clearance, non-specific biodistribution, and gastrointestinal instability. This poses major challenges for therapy targeting the intestines. Cell membrane-coated nanotechnology (CMCT) and membrane vesicle-based systems have emerged as biomimetic platforms integrating synthetic nanomaterials with naturally derived biological interfaces. These biohybrid systems inherit biological functions originating from cells, including immune evasion, prolonged circulation, lesion homing, and microenvironment-responsive interactions, through the direct transfer of intact membrane components. This review summarizes recent advances in CMCT and membrane vesicle-based strategies for intestinal drug delivery. It covers fabrication methodologies, programmable manufacturing approaches, and functional regulation enabled by diverse membrane sources and hybrid engineering designs. Applications in inflammatory bowel disease, colorectal cancer, and intestinal infections are highlighted, emphasizing key therapeutic mechanisms, such as targeting inflammation, neutralizing toxins, modulating the immune system, and regulating the microbiome. We also discuss the major challenges of translation, such as preserving membrane and coating integrity, ensuring oral stability, achieving batch reproducibility, and ensuring biosafety. Overall, this review establishes a conceptual and engineering framework to guide the transition of membrane-based nanocarriers from passive biomimicry to adaptive, clinically translatable intestinal delivery systems.