An MMP‐2 Responsive Nanotheranostic Probe Enabled Synergistic Therapy of Rheumatoid Arthritis and MR/CT Assessment of Therapeutic Response In Situ
Xuan Chen, Deshen Dai, Junping Ma, Zipei Yu, Junkai Zhao, Changqing Yi- Pharmaceutical Science
- Biomedical Engineering
- Biomaterials
Abstract
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 toward inflamed joints, and releases drugs in an MMP‐2‐responsive manner. The co‐loading of methotrexate(MTX) and tocilizumab (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 r1 relaxation rate (7.00 m