Chem-inspired synthesis of injectable metal–organic hydrogels for programmable drug carriers, hemostasis and synergistic cancer treatment

Metal-organic hydrogels (MOGs) are emerging as alternatives to metal–organic frameworks owing to advantages such as porous microstructure and flexibility, particularly in the biomedical field. In this work, injectable MOGs were developed at room temperature with zinc ions as the metal nods and 4,5-imidazole dicarboxylic acid as the organic ligand modulator by a phase-transfer strategy. The resulting MOGs enabled the programmable encapsulation and pH-responsive release of various water-soluble and water-insoluble drugs, and biomacromolecules. The prepared MOGs exhibit a microporous nanofibrous structure with low mechanical strength, and shear-thinning, injectable, and self-healing properties. Notably, high-mechanical strength self-supporting hydrogels were obtained after injection into a saline solution. This resulted in the rapid hemostatic effect of the prepared MOGs in different surgical animal models. To illustrate their drug delivery applications, doxorubicin and glucose oxidase were encapsulated into the MOGs, demonstrating the glucose–pH dual-responsive release. The drug-loaded MOGs efficiently suppressed tumor growth by the synergetic effect of tumor vascular obstruction, nutrition starvation, and chemotherapy. The injectable MOGs with controllable rheological and drug-carrying properties have promising potential for drug delivery and other biomedical applications.