MOF Hydrogel With Structurally Dynamic Properties as Stimuli-Responsive Localized Drug Delivery System for Cancer Therapy

Metal-organic framework (MOF) is an exciting class of porous biomaterial that have been considered as carrier to store and deliver therapeutic drugs. However, pure MOF similar with other nanomaterial is still limitedly used in clinic because of premature diffusion of their payloads and tissue off-targeting behavior. To figure out above challenges, we design a MOF hydrogel with structurally dynamic properties, i.e. self-healing and shear-thinning, as injectable localized drug delivery platform. To realize the presented drug encapsulating hydrogel, the doxorubicin loaded MOF (MOF@DOX) suspension is mixed with home-made bisphosphonate modified hyaluronic acid (HA-BP) polymeric binder. The dynamic coordination bonds basing hydrogel cross-linkage between the bisphosphonate groups on HA-BP macromolecule and the zinc ion on MOF particle affords the hydrogel of injectable, shear-thinning, self-healing properties. HA-BP•MOF@DOX hydrogel demonstrates pH- and ATP-responsive drug release characteristic and kills cancer cells in vitro efficiently. The animal experiments reveal HA-BP•MOF@DOX hydrogel of enhanced capability in terms of suppression tumor growth comparing with MOF@DOX group, which can be caused by the drug localization in hydrogel superstructure and sustainable release at tumor site. Therefore, the presented injectable dynamic MOF hydrogel is a promising in vivo localized drug delivery system for cancer treatment.