Progress in the application of red blood cell membrane-inspired modified metal-organic frameworks in disease treatment.

Metal-organic frameworks (MOFs) are a class of porous crystalline materials featuring tailorable architectures and versatile functions, which confer unique advantages in drug delivery and disease theranostics. However, their clinical translation remains limited by challenges such as poor stability, immunogenicity, and off-target toxicity under in vivo conditions. MOF-based nanocarriers upon biomimetic modification with RBCm are endowed with immune evasion capacity, prolonged blood circulation, and superior biocompatibility. This review systematically summarizes state-of-the-art progress in RBCm-camouflaged MOF (RBCm-MOF) systems for therapeutic applications across multiple disease types. It opens with an introduction to the structural characteristics of MOFs and the design rationale underlying biomimetic membrane coating, placing particular emphasis on the unique biological properties of RBCm that augment the core performance of such hybrid nanoplatforms. Subsequently, the review elaborates on cutting-edge advances in RBCm-MOF systems for cancer, metabolic diseases, neurological diseases and other diseases, covering therapeutic modalities including chemotherapy, phototherapy, immunotherapy, starvation therapy, and multimodal combinatorial regimens. Finally, core challenges impeding the clinical translation of this technology are critically appraised, including the structural stability of nanocarriers, scalable manufacturing, targeting accuracy, and long-term biosafety. Perspectives on future research directions are further outlined, with a focus on structural optimization, functional integration, and bench-to-bedside translation. As a smart delivery platform that integrates the inherent biological properties of natural cells with the physicochemical merits of synthetic materials, the RBCm-MOF holds tremendous promise for enabling precise, efficient, and low-toxicity therapeutic interventions.