Constructing Redox-Responsive Metal-Organic Framework Nanocarriers for Anticancer Drug Delivery

Area of Science:

• Materials Science
• Nanotechnology
• Biomedical Engineering

Background:

• Metal-organic frameworks (MOFs) are hybrid porous materials with significant potential for drug delivery.
• Existing MOF drug carriers often rely on external stimuli or surface modifications for responsiveness.
• There is a need for intrinsically responsive MOF-based drug delivery systems.

Purpose of the Study:

• To develop novel, intrinsically redox-responsive MOFs for targeted drug delivery.
• To investigate the potential of MOF-M(DTBA) (M = Fe, Al, Zr) as a drug carrier system.
• To evaluate the efficacy of curcumin-loaded MOF-Zr(DTBA) nanoparticles in cancer treatment.

Main Methods:

• Synthesis of MOF-M(DTBA) using metal nodes (Fe, Al, Zr) and 4,4 -dithiobisbenzoic acid (4,4 -DTBA) ligand.
• Characterization of MOF-Zr(DTBA) synthesized at 40 °C for drug carrier suitability.
• Encapsulation of curcumin (CCM) into MOF-Zr(DTBA) to form CCM@MOF-Zr(DTBA) nanoparticles.
• In vitro release studies and cell death assays.
• In vivo anticancer efficacy experiments.

Main Results:

• MOF-Zr(DTBA) synthesized at 40 °C exhibited suitable properties for drug delivery.
• CCM@MOF-Zr(DTBA) nanoparticles demonstrated faster in vitro curcumin release compared to free CCM.
• Enhanced cancer cell death was observed with CCM@MOF-Zr(DTBA) compared to free CCM.
• In vivo studies showed significantly higher antitumor efficacy for CCM@MOF-Zr(DTBA) than for free CCM.

Conclusions:

• A novel intrinsic redox-responsive MOF carrier, MOF-Zr(DTBA), was successfully developed.
• The disulfide bond in 4,4 -DTBA allows for glutathione-triggered drug release, particularly relevant in tumor microenvironments.
• Curcumin-loaded MOF-Zr(DTBA) nanoparticles show promising therapeutic potential for cancer treatment.
• This strategy offers new avenues for MOFs in drug delivery, molecular imaging, and theranostics.