Ca2+, pH and thermo triple-responsive mechanized Zr-based MOFs for on-command drug release in bone diseases.

We report a new approach towards the design of multi-stimuli responsive "gated scaffolds" based on the combination of capped metal-organic frameworks (MOFs) and supramolecular[2]pseudorotaxanes. These mechanized Zr-MOFs showed negligible premature release, high drug encapsulation, low cytotoxicity and good biocompatibility. Around or inside the bone tumour cells, the pH, lysosomal pH, and osteoclast pH are observed to be lowered (acidosis), and thus the resulting osteolysis increases the Ca2+ concentration (hypercalcemia). The drug release from the mechanized MOFs was triggered by the simultaneous variations of pH and Ca2+ concentration in bone tumour cells. Hyperthermia (also called thermal therapy or thermotherapy) as a popular type of cancer treatment technique can also control drug release in the above-mentioned system. This design opens up the possibility of developing smart biomaterials for bone regeneration and cancer therapy.