||Self-assembled hyaluronic acid (HA) nanoparticles have emerged as promising carriers for therapy and imaging of rheumatoid arthritis because of their selective binding affinity to CD44 which is an over-expressed receptor on inflammatory cells in rheumatoid arthritis. However, most HA-based nanoparticles reported are unable to control the release rate of encapsulated drugs in the inflammatory region. As a result, considerable amount of drugs may be released before reaching their target site, causing severe unexpected toxicity. In order to solve these problems, we have prepared HA-based nanoparticles with the pH-sensitive linker through EDC/NHS chemistry. The physicochemical characteristics of the HA nanoparticles were investigated using 1H-NMR, DLS, TEM, UV/VIS spectrophotometer and microplate reader.