Opportunities and Challenges in Biomedical Applications of Metal–Organic Frameworks

Unique chemical and physical properties of metal–organic framework (MOF) nanoparticles suggest them as promising candidates for various biomedical applications including drug delivery, biosensor, nitric oxide storage, and contrast agent. Recently, the bioactive MOFs were developed for drug delivery applications through the direct coupling of bioactive linkers such as amino acids, peptides, proteins, nucleobases, and saccharides. However, one of the major concerns with in vivo administration of the carriers is potential toxicity associated with degradation and metabolism of MOFs inside the body. Although toxicological studies of MOFs are still in its beginning stage, some parameters that may induce the toxicity in MOFs are known such as particle size, shape, types of cross-linkers and metals, functional groups, and solvent system. However, degradation mechanism, kinetics, and toxicity of MOF nanoparticles are still under study and further investigations are required to develop rationally designed MOFs with enhanced stability, biocompatibility, and therapeutic efficacy. The future efforts might be focused on the development of stable and biocompatible MOFs using bioactive linkers. This review highlights the recent advances on the synthesis, applications, and toxicity assessments of MOFs. In addition, in vivo and in vitro toxicity studies were briefly discussed with emphasis on currently available toxicology data and the future perspective of their potential clinical applications were evaluated.