Room-Temperature Synthesis of pH-Responsive MOF Nanocarriers for Targeted Drug Delivery in Cancer Therapy

Abstract

The synthesis of nanoscale metal-organic frameworks (MOFs) is emerging as a promising method for targeted drug delivery in cancer therapy. In this study, unlike conventional solvothermal methods that require high temperatures, room-temperature synthesis of two Zn-MOF-74 variants was achieved using zinc nitrate and zinc acetate with triethylamine (TEA). The use of different anions allows precise control over the morphology and particle size of the MOF, optimizing drug loading in nanocarriers. Drug loading and release were evaluated using 5-fluorouracil (5-FU) as a model drug in both aqueous and ethanolic environments. The results showed that Zn-MOF-74 prepared with zinc acetate (R_A-MOF-74) at a 1:1 drug-to-nanocarrier ratio in ethanol exhibited superior drug adsorption and release characteristics. To enhance biocompatibility and controlled release, R_A-MOF-74 nanocarriers were coated with two biodegradable polymers, sodium alginate (ALG) and polydopamine (PDA), to improve stability at low pH and enhance release control. The release profiles of 5-FU from R_A-MOF-74 and its coated samples (PDA and ALG) were evaluated at different pH levels. In uncoated R_A-MOF-74, drug release at pH 7.4 and 8 was 48.4% and 59.1%, respectively, reaching 100% at pH 1.5. For the coated samples, 5-FU@R_A-MOF-74/ALG released 19.8% and 45.9% at pH 1.5 and 8, respectively, while 5-FU@R_A-MOF-74/PDA showed 25.2% and 40.8% release at pH 7.4 and 5.5. These results clearly highlight pH-sensitive release and the role of biocompatible coatings in enhancing controlled drug release, demonstrating the potential of Zn-MOF-74 with controlled morphology for pH-responsive delivery of 5-FU in cancer therapy, paving the way for future in vivo applications.