Drug delivery and controlled release from biocompatible metal-organic frameworks using mechanical amorphization

Area of Science:

• Materials Science
• Nanotechnology
• Biomedical Engineering

Background:

• Metal-organic frameworks (MOFs) offer tunable properties for drug delivery.
• Controlling drug release kinetics from MOFs is crucial for therapeutic efficacy.
• Mechanical amorphization is a novel approach to modify MOF properties for controlled release.

Purpose of the Study:

• To investigate the use of functionalized Zr-based MOFs for controlled drug delivery.
• To evaluate the impact of linker functionalization and amorphization on drug loading and release.
• To assess the cellular uptake and therapeutic effect of MOF-loaded anticancer drugs.

Main Methods:

• Synthesis of Zr-based MOFs with varied functionalized and extended linkers.
• Loading of calcein (model drug) and α-cyano-4-hydroxycinnamic acid (anticancer drug).
• Mechanical amorphization via ball-milling.
• Confocal microscopy for cellular uptake studies.
• In vitro drug release studies.

Main Results:

• Higher loading of guest molecules in MOFs with unfunctionalized linkers.
• All MOFs demonstrated cellular penetration.
• Enhanced therapeutic effect of α-cyano-4-hydroxycinnamic acid in HeLa cells when loaded into MOFs with longer linkers.
• Sustained release of calcein over 15 days from amorphous amino-MOFs.
• No significant difference in α-cyano-4-hydroxycinnamic acid release between crystalline and amorphous forms.

Conclusions:

• A balance between MOF pore size and guest molecule size is essential for efficient sustained release via mechanical amorphization.
• Cellular internalization pathways influence MOF localization and therapeutic outcomes.
• This study provides insights for designing advanced MOFs for targeted drug delivery.