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

Area of Science:

• Materials Science
• Nanotechnology
• Chemical Engineering

Background:

• Metal-organic frameworks (MOFs) are advanced nanomaterials with tunable properties.
• MOFs show potential as drug delivery vehicles, especially for cancer therapy.
• Structural defects in MOFs can enhance drug loading and release kinetics.

Purpose of the Study:

• To engineer MOF-808 nanocarriers with controlled defects for improved cancer drug delivery.
• To investigate the impact of defects on MOF-808 stability, pH-responsiveness, and drug release efficiency.
• To evaluate the efficacy of defect-engineered MOF-808 loaded with 5-fluorouracil (5-FU) and coated with polydopamine (PDA).

Main Methods:

• Synthesis of defect-engineered MOF-808 using a mixed-ligand strategy.
• Loading of 5-fluorouracil (5-FU) into MOF-808 variants.
• Characterization of drug loading capacity (DLC) and drug release efficiency (DLE) at different pH values.
• Density functional theory (DFT) calculations to assess drug-framework interactions.
• Coating of MOF-808 with biodegradable polydopamine (PDA).
• In vitro cytotoxicity assays on MCF-7 cancer cells.

Main Results:

• MOF-808-15% exhibited enhanced pH-responsive 5-FU release, with a 22.7% increase at pH 5.5 compared to pH 7.4.
• DFT calculations confirmed strong adsorption of 5-FU onto MOF-808 (-1.13 eV).
• The PDA coating improved stability and controlled drug release, achieving 64.4% release at pH 5.5.
• The 5-FU@MOF-808-15%/PDA system demonstrated significant cytotoxicity against MCF-7 cells (77.65% inhibition).

Conclusions:

• Precise defect engineering in MOF-808 nanocarriers significantly enhances drug loading and pH-responsive release for cancer therapy.
• The biodegradable PDA coating further improves stability and controlled drug delivery.
• Defect-engineered MOFs offer a promising platform for developing efficient and biocompatible nanocarriers for advanced cancer treatments.