Metal‒organic frameworks for on-demand drug release and precision drug delivery

Abstract Metal‒organic frameworks (MOFs) are porous materials that combine high stability, large surface areas, excellent porosity, and low toxicity. The rapid development of these drugs has opened new opportunities to enhance drug efficacy with reduced adverse effects. To enhance the pharmacological effects of poorly soluble, easily degraded, low-permeability drugs can be covalently bound, adsorbed, or encapsulated in MOF nanopores. This strategy prevents premature release during transport and allows release at the target site, triggered by bond breakage or MOF structure collapse in pathological microenvironments, together with surface functional modifications. In this review, we initially summarize the antibacterial capabilities, easy functional modifications, and flexible structural properties of MOFs, as well as the standard classification of MOFs for drug delivery and their synthesis methods. We subsequently discuss functional modifications for active targeting and several pathological responsiveness tactics for targeted drug delivery, including the pH response, ion response, ATP response, redox response, magnetic reactivity, and light response. Finally, the incumbent challenges and future directions of the use of MOFs for drug delivery are proposed. This review aims to help researchers more clearly understand the properties and stimulus‐responsive mechanisms of MOFs to design more effective and targeted nanosystems for drug delivery.