Zeolitic Imidazolate Frameworks Based Anticancer Drug Delivery System Associated with Dual Action of Surface Charge and Lewis Base Ligand

Zeolitic imidazole frameworks (ZIFs), which combine the favorable characteristics of tunable porosity, controlled structure, and facile functionalization, are explored as a novel class of nanocarriers for biomedical applications. In this study, different ZIF materials are investigated, including ZIF-8, ZIF-67, ZIF-90, ZIF-92, and ZIF-108, with the same sodalite topology as the adenosine-5 '-triphosphate (ATP)-triggered drug delivery systems. Results indicated that ZIF-90 and ZIF-108 displayed good biological compatibility and efficiently accumulated in the mitochondria through competitive coordination between the metal nodes of the ZIFs and ATP, suggesting efficient intracellular delivery. With further interactions between these metal ions and ATP, the encapsulated drugs are released from the ZIF nanoparticles, thereby achieving optimal anti-tumor activity. Through a systematic evaluation of the physicochemical properties of different ZIFs, it demonstrates that the surface charges of ZIFs have a significant impact on the cytotoxicity of cells, whereas the Lewis basicity of imidazole-based ligands plays an essential role in the competitive coordination between the metal ions and ATP. These findings provide a potential method for screening ZIFs based nanocarriers with minimal toxicity and explain the different delivery efficiencies of these materials with similar topologies. Different zeolitic imidazolate frameworks (ZIFs) with the same sodalite topology are employed as model nanocarriers to investigate cell cytotoxicity, cellular uptake of nanoparticles, and release of anticancer drugs. These nanocarriers show therapeutic efficacy that is correlated with the surface charges of the ZIFs and the Lewis basicity of the imidazole-based ligands. image