Self-Disassembling Macroporous Metal-Organic Framework-Based Micromotors with Magnetically Controlled Motion for Sequential Drug Release.

Herein, the synthesis of macroporous zeolitic imidazole framework (ZIF)-based magnetic micromotors (MMs) for the dual encapsulation of 5-fluorouracil (5-FU) and doxorubicin (DOX), with pH-triggered release is described. The MMs are synthesized in methanolic solutions, using superparamagnetic iron oxide nanoparticles (Fe₃O₄) as seeding agents and magnetic engines. The macroporous structure facilitates the loading of high doses of 5-FU, while DOX is docked on the surface of the MMs. This results in release rates of 72.8 µg mg MMs⁻¹ of 5-FU and 3 µg mg MMs⁻¹ of DOX. The magnetic motion of the MMs enables targeted delivery to predefined locations, allowing interaction with cancer cells in the culture medium. Under acidic conditions, DOX becomes protonated and is released from the surface of the micromotors, demonstrating rapid-release kinetics. Simultaneously, the ZIF-8 structure degrades under these conditions, enabling the sustained release of 5-FU for continuous treatment. This dual-delivery, pH-induced mechanism is demonstrated in vitro using Caco-2 cells as a relevant biological model, revealing a decrease in viability and diffusion of the drugs released into the cells. This is the first magnetic metal-organic framework (MOF)-based MM that is pH-sensitive and capable of sequentially releasing two drugs.