Mesoporous Rod‐Like Metal‐Organic Framework with Optimal Tumor Targeting Properties for Enhanced Activatable Photodynamic Therapy

Abstract Nanoscale metal‐organic frameworks (nMOFs) have shown great potential in the highly effective delivery of exogenous drugs and imaging agents for biomedical applications, and rod‐like nanomaterials with superb loading capability have demonstrated broad versatility to tumor imaging and tumor‐targeted drug delivery. However, owing to difficulties in their fabrication, nMOFs with both rod‐like shape and mesoporosity for tumor imaging or tumor‐targeted cargo delivery are largely unexplored. Herein, a nanoscale rod‐like [{Cu 2 (ndc) 2 (dabco)] n (Cu‐MOF), a copper(II) nMOF, is successfully endowed with mesoporosity via defect engineering. Owing to the mesopores, the as‐synthesized defective rod‐like Cu‐MOF is able to load an aggregation‐induced‐emission (AIE) photosensitizer (PS) with inhibited sensitization at high loading weight percentage. In vitro and in vivo experiments demonstrate that the rod‐like Cu‐MOF can afford the AIE PS payload with enhanced tumor targeting specificity and penetration depth. After optimal tumor enrichment and cancer cell uptake, Cu(II) in the defective Cu‐MOF efficiently depletes intracellular glutathione and causes dissociation of the Cu‐MOF to release the PS payload and recover its efficient reactive oxygen species generation. Concomitantly, bright fluorescence is afforded by the AIE PS during delivery, contributing to image‐guided cancer‐cell‐activated photodynamic therapy with enhanced therapeutic effects.