Synthesis of 'dual-key-and-lock' drug carriers for imaging and improved drug release

Abstract

In this work, a 'dual-key-and-lock' drug carrier was designed to respond to the tumor microenvironment (TME). A core-shell Fe-MOF@ZIF-8 was synthesized, with ZIF-8 as the shell (the first lock) to encapsulate catalase (CAT), and the Fe metal-organic framework (MOF) as the core (the second lock) to encapsulate the anticancer drug doxorubicin (DOX). Fe-MOF@ZIF-8 takes advantage of the TME-which includes a high concentration of H₂O₂, a weakly acidic environment and hypoxia-to achieve efficient cancer therapy. With the pH response, ZIF-8 and Fe-MOF are degraded in turn to release CAT and DOX, just like 'pH stimulation', as a key to open the two locks in turn. The released CAT reacts with the rich H₂O₂ in the tumor to produce O₂ to regulate hypoxia, thereby improving the anticancer efficiency of the released DOX. The different cytotoxicity to L-02 cells and HeLa cells of Fe-MOF@ZIF-8 shows Fe-MOF@ZIF-8 is only harmful to cancer cells and is not harmful to normal cells. The reason is that the Fe²⁺/Fe³⁺ in Fe-MOF interact with the rich H₂O₂ in cancer cells to generate hydroxyl radicals (ċOH), which is proved by the color of the solution of 3,3',5,5'-tetramethylbenzidine turning blue. After loading of the drug and CAT, Fe-MOF@ZIF-8 can release CAT, DOX and ċOH in response to the TME, thus killing more HeLa cells. Therefore, synthesis of 'dual-key-and-lock' drug carriers responsive to the TME is a promising strategy for cancer treatment.