Tuned Cationic Dendronized Polymer: Molecular Scavenger for Rheumatoid Arthritis Treatment

Cell‐free deoxyribonucleic acid (cfDNA) released from either dead or damaged cells serves as a key autoantigen in rheumatoid arthritis (RA). They can be recognized by nucleic acid (NA) sensors such as the toll‐like receptor (TLR), leading to activation of the innate immune system and chronic inflammation. Developed here is a cationic molecular scavenger, by screening cationic dendronized polymers, which eliminates cfDNA and inhibits TLR recognition and nucleic‐acid‐induced inflammation. The structure–property study demonstrates that toxicity, NA binding capacity, and biodistribution could be balanced to achieve maximum therapeutic effect by exquisite control of the molecular structure. In addition, the optimized cationic polymer effectively inhibited joint swelling, synovial hyperplasia, and bone destruction in collagen‐induced arthritis (CIA) rat models. The results offer support for synthetic polymers offering new paradigm in autoimmune disease treatment. Scavenger hunt: Screening of cationic dendronized polymers led to scavengers that could eliminate cell‐free DNAs and inhibit Toll‐like receptor recognition and nucleic‐acid‐induced inflammation. The scavengers having longer backbones and higher charge densities were preferentially accumulated in the inflammatory joints of arthritis rats. As a result, joint swelling, synovial hyperplasia, and bone destruction were inhibited.