A MMP-2 Responsive Nanotheranostic Probe Enabled Synergistic Therapy of Rheumatoid Arthritis And Mr/Ct Assessment of Therapeutic Response in Situ

This study reports a facile and green synthesis of a new multifunctional nanotheranostic probe for the synergistic therapy of rheumatoid arthritis (RA) and in situ assessment of therapeutic response. The probe is synthesized through a one-step self-assembly of two exquisitely designed peptide-amphiphilic block copolymers (PEG-DTIPA-KGPLGVRK-MTX and Pal-GGGGHHHHD-TCZ) under mild conditions , requiring minimal energy input. The resultant probe demonstrates excellent biocompatibility, water-solubility and colloidal stability . It exhibits a strong IL-6R targeting ability towards inflamed joints, and releasees drugs in an MMP-2-responsive manner. The co-loading of MTX and TCZ into the probe enables synergistic RA therapy with improved efficacy by simultaneously decreasing the activity of adenosine synthetase and interfering with the binding of IL-6 to its receptor. In addition, the resultant probe exhibits a high r relaxation rate (7.00 mM s ) and X-ray absorption capability (69.04 Hu mM ), enabling sensitive MR and CT dual-modal imaging for simultaneous evaluation of synovial thickness and bone erosion. Both in vitro experiments using lipopolysaccharide-treated RAW264.7 cells and in vivo experiments using collagen induced arthritis mice demonstrate the probe's high effectiveness in synergistically inhibiting inflammation. This study provides new insights into RA theranostics, therapeutic monitoring, the design of multifunctional theranostic probes and beyond. This article is protected by copyright. All rights reserved.