Metal-organic frameworks (MOFs) have become well-adaptable and versatile porous materials with a variety of potential applications in drug delivery, catalysis, sensing, and environmental remediation. However, utilization in biological systems and the environment is limited due to concerns about their chemical stability and potential toxicological behavior. The review assesses the specific factors that determine MOF toxicity while combining quantitative data from in vitro, in vivo ad environmental studies. In particular, evidence suggests Cu- and Co-based MOFs create excessive ROS via Fenton-type pathways while Zn- based MOFs, such as ZIF-8, demonstrated dose-dependent cytotoxicity due to rapid Zn 2+ release under acidic conditions. Linker degradation byproducts resulted in interference with metabolism and an inflammatory response. Nanoparticles with sizes less than 100 nm displayed additional cellular uptake, mitochondrial dysfunction, and developmental issues in zebrafish embryos. Environmental exposure also revealed some degree of phytotoxicity and some shifts in microbial communities, as exemplified by biomass loss in pea seedlings exposed to MOF-199. While the available data appear to increase, the gaps in knowledge are still significant regarding long-term exposures, biodegradation considerations of the linker, bio-distribution aspects on the nanoscale, and toxicological evaluation protocols to determine standardization of MOF materials. This review summarizes existing mitigation strategies—including biocompatible metal selection, structural stabilization, and coatings with polymeric material that have decreased cytotoxity in controlled settings. As a whole, this review highlights an immediate need for mechanistic, long-term, and regulatory work to facilitate the development of safe, responsible, and sustainable use and translation of MOFs in the biomedical and industrial spheres.
Tripathy et al. (Tue,) studied this question.