Pei-Hong Tong, Xi-Le Hu, Kai-Cheng Yan, Xiao-Shuai Yuan, Tony D James, Hong-Yang Wang, Xiao-Peng He
As cutting-edge porous materials, the properties of metal-organic frameworks (MOFs) are governed by their metal nodes and organic linkers, as well as the assembly mode of these subunits. This allows the loading capacity of MOFs for small-molecule drugs to be readily tailored by rationally adjusting their structures and physicochemical properties. Furthermore, the introduction of additional functional groups into MOFs can enable the stimuli-responsive release of small-molecule drugs, thus rendering MOFs promising candidates for small-molecule drug delivery. With this perspective, we summarize the advances in the construction of MOF-based small-molecule drug delivery carriers and analyze the advantages and limitations of the various loading strategies for small-molecule drugs. We also introduce drug release mechanisms and their application for the targeted treatment of various human diseases. In particular, this perspective describes how the corresponding drug-loading strategies should be selected based on the inherent physicochemical properties of the small-molecule drugs and the specific biomedical application, in order to facilitate clinical translation.