Toxicity and Biocompatibility of Metal–Organic Frameworks: A Comprehensive Review of Biomedical Applications Publisher



Azadvar S ; Saate H ; Khalilzadehiranighadam MM ; Samadi N ; Sotoudegan F
Source: Journal of Drug Delivery Science and Technology Published:2026

Abstract

Drug delivery, imaging, biosensing, and therapeutic interventions are among the many biomedical applications for which metal-organic frameworks (MOFs) are highly desirable due to their remarkable structural tunability, large surface areas, and controllable functionality. Despite their tremendous potential, concerns remain regarding their toxicity, stability, and biocompatibility. The factors affecting MOF toxicity, including metal ion composition, organic linker type, particle size, surface charge, and degradation behavior, as well as their intricate interactions within biological systems, are all thoroughly evaluated in this work. This work also investigates novel approaches to improving biocompatibility, such as the use of bioresorbable metals, green production pathways, and surface modification methods that enhance physiological stability and reduce unfavorable cellular reactions. The review highlights current developments in predictive toxicology, computational modeling, and in vitro/in vivo research that together increase our knowledge of MOF–biological interface dynamics. Additionally, it draws attention to new design paradigms intended to create multifunctional, stimuli-responsive MOFs for targeted and precise treatments. This work highlights the revolutionary potential of MOFs while promoting standardized toxicity evaluations and responsible design approaches through the integration of materials science, nanotechnology, and biomedical engineering viewpoints. Overall, this work advances the sustainable and safe use of MOFs in biomedicine and paves the way for their eventual translation into intelligent, biocompatible, and clinically relevant therapeutic platforms. Copyright © 2026. Published by Elsevier B.V.