Given the high potential of metal-organic frameworks (MOFs) to be used as delivery carriers for drug molecules, it is crucial to evaluate the potential of MOFs coupled with the molecular targeted ligands and explore as a targeted drug carriers.The zinc MOFs was firstly synthesized and then conjugated with the folic acid via postsynthetic modifications methods (Figure 1).Their efficiency as targeted-drug carriers will test with 5-fluorouracil (5-FU).We observe the in vitro release behavior and evaluate the cytotoxic effects of using the MTT assay.Furthermore, the ability of folate targeting ligand was tested by competition assay.The successful synthesis of MOFs conjugated with folic acid was confirmed by ESI-MS analysis and 1H NMR and SEM images revealed that the targeted-drug carriers had an average diameter around 200 nm.The systems showed remarkable 5-FU loading efficiency, as exceptionally high (20.4 wt %) and is almost four times higher than the system of polymer nanoparticles (5~6 wt %).The folate-targeted MOFs showed a higher antiproliferative activity and a higher selectivity than the non-targeted ones when studied against KB cell line that over-expressed the folic acid receptor.The cancer-targeting design could be a good strategy to deliver the anticancer drugs, since they could provide preferential accumulation of drug delivery systems in the tumor-bearing organ, enhance the selective killing abilities against cancer cells, and at the same time, reduce the toxicity toward normal cells.Given their relatively lower induced toxicity and exceptionally high drug loading efficiency, folate-targeted MOFs may be candidates for further evaluation as a chemotherapeutic agent for human cancers.