Intelligent dual responsive modified ZIF-8 nanoparticles for diagnosis and treatment of osteoarthritis

Abstract Reactive oxygen species (ROS) are highly expressed in osteoarthritis (OA). In this study, resveratrol (RES)- and CellROX-loaded zeolite-based imidazolium salt framework-8 (ZIF-8) nanoparticles (NPs) immobilized with methoxy poly (ethylene glycol) with thioketal grafting (mPEG-TK) were synthesized for OA treatment. Once applied to OA joints, the protective coating of mPEG-TK outside the ZIF-8 NPs was depolymerized in response to the relatively high ROS level. Immediately, ROS turned on the fluorescence of CellROX inside the ZIF-8 NPs to diagnose and monitor the OA process. Meanwhile, RES released from NPs and stimulated the transformation of macrophage polarization from the M1 phenotype (pro-inflammatory) to the M2 phenotype (anti-inflammatory). Our prepared NPs can inhibit inducible nitric oxide synthase (iNOS), thus decreasing NO production and increasing H2O2 production. The results indicated that when the modified NPs were used for OA treatment in rats, the improvement of OA could be detected by decreasing fluorescence after 4 weeks of injection. The fluorescence results were consistent with those of the tissue sections. The NPs developed in this study displayed dual functions as fluorescence detection and ROS regulation therapy, which would provide new paths for OA diagnosis and treatment.