Coordination‐Dissociation Induced T1‐Weighted Magnetic Resonance Imaging Responses in a spn‐Type MOF for Potential Drug Release Monitoring

Abstract Developing novel nanoplatforms capable of monitoring drug release by identifiable magnetic resonance imaging (MRI) responses is a great promising yet challenging task. Here, a novel isoreticular chemistry strategy is introduced to enable a spn ‐type metal–organic framework (MOF) with T 1 ‐weighted MRI turned‐on response to the drug release via a coordination‐dissociation process. Post‐synthetic functionalization endows the structure with a high longitudinal relaxivity r 1 of 12.63 m m −1 s −1 as well as abundant accessible coordination sites to catch carboxylate probes and drugs. Mechanism studies reveal a size‐dependent decrease in relaxivity as the coordinated carboxylate probes increase in size, with bulk benzoic acid showing the largest identifiable reduction at 71%. In vitro model studies further validate the MRI signals response respectively by coordinating four drugs with aromatic carboxylate groups. Finally, in vivo experiments confirm the feasibility of using this coordination‐dissociation‐induced MRI response to monitor drug release. This proof‐of‐principle study demonstrates a practical pathway for designing MOF‐based nanoplatforms for responsive MRI, paving the way for enhanced non‐invasive drug monitoring techniques.