Drug-Embedded Nanovesicles Assembled from Peptide-Decorated Hyaluronic Acid for Rheumatoid Arthritis Synergistic Therapy.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes endless pain and poor quality of life in patients. Usage of a lubricant combined with anti-inflammatory therapy is considered a reasonable and effective approach for the treatment of RA. Herein, inspired by glycopeptides, a peptide-decorated hyaluronic acid was synthesized, and the grafted Fmoc-phenylalanine-phenylalanine-COOH (FmocFF) peptide self-assembled with β-sheet conformations could induce the folding of polymer molecular chains to form a vesicle structure in aqueous solution. The hydrophobic anti-inflammatory drug curcumin (Cur) could be embedded in the vesicle walls through π-π interactions with the FmocFF peptide. Furthermore, the inflammation suppression function of the Cur-loaded vesicles both in vitro and in vivo was demonstrated to be an effective treatment for RA therapy. This work proposes new insights into the folding and hierarchical assembly of glycopeptide mimics, providing an efficient approach for constructing intelligent platforms for drug delivery, disease therapy, and diagnostic applications.