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

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.