Iron-based metal-organic frameworks (MOFs) have been reported to have great potential for encapsulating doxorubicin hydrochloride (DOX), which is a frequently used anthracycline anticancer drug. However, developing a facile approach to realize high loading capacity and efficiency as well as controlled release of DOX in MOFs remains a huge challenge. Herein, we synthesized water-stable MIL-101(Fe)-C4H4 through a microwave-assisted method. It was found the nano-MOFs acted as nanosponges when soaked in a DOX alkaline aqueous solution with a loading capacity experimentally up to 24.5 wt %, while maintaininga loading efficiency as high as 98%. The mechanism of the interaction between DOX and nanoMOFs was investigated by absorption spectra and density functional theory (DFT) calculations, which revealed that the deprotonated DOX was electrostatically adsorbed to the unsaturated Fe3OCl(COO)6·H2O (named Fe3 trimers). In addition, the as-designed poly(ethylene glycol-co-propylene glycol) (F127) modified nanoparticles (F127-DOX-MIL) could be decomposed under the stimulation of glutathione (GSH) and ATP. As a result, DOX and Fe(III) ions were released, and they could undergo a Fenton-like reaction with the endogenous H2O2 to generate the highly toxic hydroxyl radical (·OH). The in vitro experiments indicated that F127-DOX-MIL could cause remarkable Hela cells inhibition through chemotherapy and chemodynamic therapy. Our study provides a new strategy to design a GSH/ATP-responsive drug-delivery nanosystem for chemo/chemodynamic therapy.
Keywords: doxorubicin hydrochloride; iron-based metal−organic framework; loading capacity; loading efficiency.