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

Metal-organic frameworks (MOFs), which are a unique class of hybrid porous materials built from metal ions and organic ligands, have attracted significant interest in recent years as a promising platform for controlled drug delivery. Current approaches for creating MOFs-based responsive drug carriers involve encapsulation of stimuli-responsive compositions into MOFs or postsynthetic surface modification with sensitive molecules. In this study, we developed a novel intrinsic redox-responsive MOFs carrier, MOF-M(DTBA) (M = Fe, Al or Zr) by using iron, aluminum, or zirconium as metal nodes and 4,4'-dithiobisbenzoic acid (4,4'-DTBA) as the organic ligand. The disulfide bond in 4,4'-DTBA is cleavable by glutathione (GSH), which is often overexpressed in tumor cells. It was found that MOF-Zr(DTBA) synthesized at 40 °C displayed the appropriate size and properties as a drug carrier. By incorporating curcumin (CCM) into MOF-Zr(DTBA), CCM@MOF-Zr(DTBA) nanoparticles were obtained that displayed a faster releasing behavior in vitro and enhanced the cell death compared with free CCM. The in vivo anticancer experiments indicate that CCM@ MOF-Zr(DTBA) exhibits much higher antitumor efficacy than free CCM. This strategy for constructing responsive MOFs-based nanocarriers might open new possibilities for the application of MOFs in drug delivery, molecular imaging, or theranostics.