Programmable Drug Release from a Dual-Stimuli Responsive Magnetic Metal-Organic Framework

Along with the increasing incidence of cancer and drawbacks of traditional drug delivery systems (DDSs), developing novel nanocarriers for sustained targeted-drug release has become urgent. In this regard, metal-organic frameworks (MOFs) have emerged as potential candidates due to their structural flexibility, defined porosity, lower toxicity, and biodegradability. Herein, a FeMn-based ferromagnetic MOF was synthesized from a preassembled Fe2Mn(mu 3-O) cluster. The introduction of the Mn provided the ferromagnetic character to FeMn-MIL-88B. 5Fluoruracil (5-FU) was encapsulated as a model drug in the MOFs, and its pH and H2S dual-stimuli responsive controlled release was realized. FeMn-MIL-88B presented a higher 5-FU loading capacity of 43.8 wt % and rapid drug release behavior in a tumor microenvironment (TME) simulated medium. The carriers can rapidly release loaded drug of 70% and 26% in PBS solution (pH = 5.4) and NaHS solution (500 mu M) within 24 h. The application of mathematical release models indicated 5-FU release from carriers can be precisely fitted to the first-order, second-order, and Higuchi models of release. Moreover, the cytotoxicity profile of the carrier against human embryonic kidney cells (HEK293T) suggests no adverse effects up to 100 mu g/mL. The lesser toxic effect on cell viability can be attributed to the low toxicity values [LD50 (Fe) = 30 gmiddotkg(-1), (Mn) = 1.5 gmiddotkg(-1), and (terephthalic acid) = 5 gmiddot kg(-1)] of the MOFs structural components. Together with dual-stimuli responsiveness, ferromagnetic nature, and low toxicity, FeMnMIL-88B MOFs can emerge as promising carriers for drug delivery applications.