Porosity Modification in MOF Nanocarriers for pH-Responsive Drug Delivery in Cancer Therapy

Metal-organic frameworks (MOFs) have emerged as promising nanocarriers for targeted drug delivery, particularly in cancer therapy. Introducing structural defects into MOFs significantly enhances their drug-loading capacity and release efficiency. This study explores porosity modification through defect-engineered MOF-808 nanocarriers, synthesized via a mixed-ligand strategy, to enhance the stability, pH-responsiveness, and drug delivery efficiency for cancer therapy. The modified MOF-808 variants were loaded with 5-fluorouracil (5-FU) in ethanol and water to optimize the drug loading capacity (DLC) and drug release efficiency (DLE). Among them, MOF-808-15% demonstrated a drug release of 57.7% at pH 7.4 and 70.8% at pH 5.5, showing a 22.7% increase under acidic conditions, which is ideal for pH-responsive drug delivery. Density functional theory (DFT) calculations revealed a strong adsorption energy (-1.13 eV) between MOF-808 and 5-FU, confirming effective drug-framework interactions. Additionally, a biodegradable polydopamine (PDA) coating enhanced the stability and enabled controlled drug release in acidic environments. In the 5-FU@MOF-808-15%/PDA system, 64.4% of the drug was released at pH 5.5, marking a 21.97% improvement compared with neutral conditions. Cytotoxicity assays on MCF-7 cells showed 77.65% inhibition, comparable to free 5-FU (80.4%) at 400 μg/mL. These findings demonstrate that precise defect engineering in MOFs can yield highly efficient and biocompatible drug nanocarriers, paving the way for advanced controlled-release cancer therapies.