pH and H₂S Dual-Responsive Magnetic Metal-Organic Frameworks for Controlling the Release of 5-Fluorouracil

Along with the increasing cancer incidence, developing suitable drug delivery systems (DDSs) is becoming urgent to control drug release and further enhance therapeutic efficiency. Herein, a Fe-Zn bimetallic MOF-derived ferromagnetic nanomaterial was synthesized by a one-step method. The successful preparation of ferromagnetic Fe-ZIF-8 was verified by scanning electron microscopy, powder X-ray diffraction, Brunauer-Emmett-Teller, X-ray photoelectron spectroscopy, and physical property measurement system characterizations. Furthermore, the release behaviors of 5-FU from the ferromagnetic carrier were investigated in a simulative cancer microenvironment of PBS buffer solution (PBS = phosphate-buffered saline, pH = 5.8) and NaHS solution. The vehicle in PBS solution of pH = 5.8 and NaHS solution of 500 μM can rapidly release 5-FU with the cumulative release percentages of 68 and 36%, respectively, within two hundred minutes. The release mechanism in the weak acid environment can be mainly attributed to the decomposition of the Fe-ZIF-8. However, the strong interaction between Zn and Fe atoms in Fe-ZIF-8 and the S atom in H₂S plays an important role in the release process in the simulated H₂S cancer microenvironment. The investigation of release kinetic models indicates that the 5-FU release in the PBS solutions and NaHS solution of 500 μM can be accurately fitted by a second-degree polynomial model and first-order model, respectively. In addition, the decomposition products, zinc, iron, and 2-MeIM, are endogenous and show low toxicity values [LD₅₀ (Zn) = 0.35 g·kg^-1, LD₅₀ (Fe) = 30 g·kg^-1, and LD₅₀ (2-MeIM) = 1.4 g·kg^-1]. Therefore, the low-toxicity, pH and H₂S dual-stimuli-responsive, and ferromagnetic nature make the obtained Fe-ZIF-8 an ideal candidate in the field of bioactive molecule delivery.