Metal-organic framework-based hydrogel with structurally dynamic properties as a stimuli-responsive localized drug delivery system for cancer therapy

Metal-organic framework (MOF) is an exciting class of porous biomaterials that have been considered as a carrier to store and deliver therapeutic drugs. However, similar to other nanomaterials , the application of MOF in clinical settings is still limited because of premature diffusion of their payloads and tissue off-targeting behavior. To overcome these challenges, we designed an MOF-based hydrogel with structurally dynamic properties, i.e. , self-healing and shear-thinning, as an injectable localized drug delivery platform. The drug-encapsulating MOF hydrogel is formed through a dynamic coordination bond cross-linkage between a doxorubicin-loaded MOF ( [email protected] ) particle and a homemade bisphosphonate-modified hyaluronic acid (HA-BP) polymeric binder. The HA-BP· [email protected] hydrogel demonstrates pH- and ATP-responsive drug release characteristic and efficiently kills cancer cells in vitro . The animal experiments reveal that the HA-BP· [email protected] hydrogel has enhanced capability in terms of tumor growth suppression as compared to the [email protected] group, which can be attributed to drug localization in hydrogel superstructure and sustained release at the tumor site. The presented injectable dynamic MOF-based hydrogel is a promising in vivo localized drug delivery system for cancer treatment. Herein, we report the self-healing and shear-thinning of MOF-based drug carrier cross-linked by coordinate bonds for the first time and provide new insights and a facile chemical strategy for designing and fabricating MOF-based biomaterials by using bisphosphonate-zinc interaction. Statement of significance Bisphosphonate-zinc interaction is a facile chemical strategy to cross-link metal-organic framework (MOF)-based hydrogel. The presented MOF-based hydrogel demonstrates structurally dynamic properties, including smooth injectability, self-healing, and shear-thinning. The developed MOF-based hydrogel possesses pH- and ATP-responsive drug release characteristic and kills cancer cells in vitro efficiently. The dynamic MOF-based hydrogel shows enhanced in vivo anticancer activity as compared to pure MOF particles. Self-healing and shear-thinning of metal-ligand cross-linked MOF-based drug delivery system are reported for the first time, thus providing new insights for the design and fabrication of MOF-based biomaterials.