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.

Design and fabrication of intracellular therapeutic cargo delivery systems based on nanomaterials: current status and future perspectives

“…Interestingly, the photosensitizer in this work obsessed a monitoring function, as it provided bright fluorescence during the delivery after intravenous injection. 323 PTT is another an emerging therapy that has drawn attention in recent years, which refers to the method of killing cells by producing high temperature under the irradiation of NIR light with photothermal agents. Hu et al prepared polydopamine (PDA)-doped hollowed dendritic MSNs, which exhibited excellent photothermal effect under near-infrared laser irradiation.…”

“…Interestingly, the photosensitizer in this work obsessed a monitoring function, as it provided bright fluorescence during the delivery after intravenous injection. 323…”

Inorganic‐Based Aggregation‐Induced Luminescent Materials: Recent Advances and Perspectives

“…Reproduced with permission. [ 114 ] Copyright 2021, Wiley‐VCH GmbH. E) Schematic illustration of the fluorescence enhancement strategy of GSH‐Au NCs@ZIF‐8.…”

Heterostructured hybrids of metal–organic frameworks (MOFs) and covalent–organic frameworks (COFs)

“…196 The exquisitely designed nanoMOFs and COFs with small sizes (approximately 200–300 nm) exhibit good biocompatibility and biodegradability, thus showing potential applications in cancer therapy. 197 Different types of MOFs containing metal ions or organic ligands with catalytic performances, such as Cu-MOF, 198,199 NH 2 –MIL-88B (Fe), 200,201 Mn-MOF, 202,203 UiO-66/Zr-MOF, 204–207 and porphyrinic-based MOFs, 208–210 have been explored not only as anticancer drug carriers but also as catalysts for chemodynamic therapy (CDT) and photodynamic therapy (PDT). COFs have unique advantages, such as high crystallinity, inherent pores, and large specific surface areas, which remarkably improve their loading ability toward different cancer drugs such as ibuprofen, 211 DOX, 212 5-fluorouracil, 213 captopril, 214 and curcumin, 215–217 as well as near infrared (NIR) dyes.…”