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

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.