Recent advances in MOF-based drug delivery: Disease-specific strategies and clinical perspectives

Metal-organic frameworks (MOFs) have advanced from gas storage and catalysis to become programmable biomedical carriers, combining high surface area, tunable porosity, and modular metal-ligand chemistry for precise drug delivery. Yet most existing reviews are organized around synthetic strategies or individual framework structures and remain dominated by oncology, leaving the logic that links MOF design to specific disease environments fragmented. This review addresses that gap by reorganizing the field around disease biology rather than framework type, providing a unified, mechanistic account of how framework composition, particle size, and surface functionalization can be tuned to distinct pathological microenvironments to trigger release through pH, redox gradients, reactive oxygen species (ROS), enzymatic activity, or temperature. In cancer, we examine how MOFs exploit tumor-microenvironment (TME) hallmarks to coordinate chemotherapy with photodynamic, photothermal, and chemodynamic modalities. Beyond oncology, we consolidate scattered advances in infectious-disease control, tissue regeneration, and immunomodulation, and identify neurology, where blood-brain barrier (BBB) transport, oxidative-stress regulation, and enzyme-triggered release are decisive as an emerging frontier. Recognizing that clinical translation remains the central bottleneck, we critically assess scalable synthesis, particle-size control, in-vivo stability, endosomal escape, reproducible biodegradation, and comprehensive safety evaluation. Building on this analysis, we propose explicit design principles and reporting standards intended to accelerate the move from laboratory proof-of-concept to clinically viable therapeutics. By framing MOF chemistry within a disease-specific context, this review offers a rational, testable, and translationally grounded roadmap that positions MOFs as hybrid materials uniting chemical precision with biological purpose.