Affiliation:
1. Division of Orthopaedics and Traumatology Department of Orthopaedics Nanfang Hospital Southern Medical University Guangzhou 510515 P. R. China
2. Department of Orthopaedics and Traumatology The Seventh Affiliated Hospital Southern Medical University Foshan 528244 P. R. China
3. PCFM Lab of Ministry of Education School of Material Science and Engineering Sun Yat‐Sen University Guangzhou 510275 P. R. China
4. Department of Radiology The Third Affiliated Hospital of Sun Yat‐sen University Guangzhou 510630 P. R. China
Abstract
AbstractRheumatoid arthritis (RA) progression involves multiple cell types, and sequential drug action on target cells is necessary for RA treatment. Nanocarriers are widely used for RA treatment; however, the targeted delivery and on‐demand release of multiple drugs remains challenging. Therefore, in this study, a dual‐sensitive polymer is developed using chondroitin sulfate (CS) for the co‐delivery of the cartilage repair agent, glucosamine (GlcN), and anti‐inflammatory drug, tofacitinib (Tof). In the joint cavity, acidic pH facilitates the cleavage of GlcN from CS polymer to repair the cartilage damage. Subsequently, macrophage uptake via CS–CD44 binding and intracellular reactive oxygen species (ROS) mediate conversion of (methylsulfanyl)propylamine to a hydrophilic segment jointly triggered rapid Tof/GlcN release via micelle disassembly. The combined effects of Tof, GlcN, and ROS depletion promote the M1‐to‐M2 polarization shift to attenuate inflammation. The synergistic effects of these agents against RA are confirmed in vitro and in vivo. Overall, the dual pH/ROS‐sensitive CS nanoplatform simultaneously delivers GlcN and Tof, providing a multifunctional approach for RA treatment with synergistic drug effects.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Guangdong Province
Subject
Biomaterials,Biotechnology,General Materials Science,General Chemistry