Redox-responsive tumor targeted dual-drug loaded biocompatible metal–organic frameworks nanoparticles for enhancing anticancer effects
Chang Liu, Xiaoyu Xu, Junnian Zhou, Jiaqi Yan, Dongqing Wang, Hongbo Zhang
Abstract
Abstract Metal–organic frameworks (MOFs) have proven to be a promising class of drug carriers due to their high porosity, crystalline properties with defined structure information, and abundant surface chemistry for further functionalization. However, there has not been extensive research on MOF-based drug carriers with stimuli-responsive, dual-drug delivery, and tumor targeting functions. Here, we demonstrate the strategy of constructing a redox responsive and tumor-targeted MOF as dual-drug carrier by anchoring functional disulfide anhydride and folic acid molecules to the organic links of MOFs, respectively. The MOF composites show the controlled release of loaded 5-fluorouracil (5-FU) entrapped within UiO-66-NH 2 nanostructures modified with dichloroacetic acid, which acts as a synergistical drug to 5-FU in cancer cells. In addition, the overexpressed GSH in cancer cells attacks the thiolate moiety and is oxidized in the process as it cleaves the disulfide bonds, thereby achieving redox stimuli-responsive drugs release in MOFs. The confocal laser scanning microscopy further proved that conjugation of folic acid to the MOF surface can significantly enhance the targeting uptake of cancer cells. This work paves the way to the construction of stimuli responsive tumor-targeted Nano MOF based drug carriers with potential for cancer therapies.