The Application of Metal–Organic Frameworks as Drug Delivery Systems: From the Perspective of Molecular Dynamics Simulations

Metal-organic frameworks (MOFs) have emerged as a promising class of nanomaterials for drug delivery due to their exceptionally high surface area, tunable pore structures, and chemical versatility. However, conventional experimental techniques cannot fully capture atomic-scale drug-carrier interactions or transient diffusion processes within MOF pores. Molecular dynamics (MD) simulation, a computational technique that tracks atom-level movements over time, has thus become indispensable for probing these microscopic mechanisms. This review introduces the fundamentals of MD simulation and comprehensively examines how MD simulation reveals drug adsorption mechanisms, functionalization effects, and release kinetics in MOF-based delivery systems. Then, it systematically compares major MOF families including isoreticular metal-organic frameworks, zeolitic imidazolate frameworks, Materials of Institute Lavoisier Frameworks, University of Oslo Frameworks, and porous coordinated networks and highlight their distinct host-guest interactions and stimuli-responsive behaviors. The integration of multiscale modeling and machine learning further enhances predictive capabilities for carrier design. By establishing MD simulation as a fundamental tool for understanding nanoscale drug-carrier interactions, this review provides a theoretical foundation for developing efficient, stable, and responsive MOF-based nanocarriers, advancing the field of precision nanomedicine.