Hydrazone modified nanoscale metal-organic frameworks as pH responsive nanoplatforms for cancer therapy

Practical clinical applications of chemotherapeutic drug are limited due to inevitable drawbacks such as low water solubility, big side effect and poor therapeutic efficiency. To overcome these drawbacks, we developed a novel nanoscale metal-organic framework (nMOFs)-based pH-responsive drug delivery system designed for efficient cancer therapy. In this work, a zirconium-based nMOFs UiO-66 was synthesized, and its surface was engineered to convert partial amino groups to hydrazone groups through stepwise organic transformations. Subsequently, the anticancer agent doxorubicin (DOX) served as a therapeutic drug and a fluorescent label was loaded through acid-labile hydrazone linkage to yield UiO-66-DOX. Acidic pH conditions (such as those surrounding tumor cells) catalyzed the hydrolysis of the hydrazone linkage and promoted the DOX release. These novel pH-sensitive drug delivery system will help to achieve safe delivery of the very cytotoxic chemotherapeutic drug (such as DOX), allowing to reduce the therapeutic dose and minimizing drug secondary effects.