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

Abstract

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 peptidedecorated hyaluronic acid was synthesized, and the grafted Fmocphenylalanine-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.

Nitric oxide-scavenging hyaluronic acid nanoparticles for osteoarthritis treatment

“…Hyaluronic acid (HA), an essential component in healthy joints, was selected as the polymer for the NSc conjugation. HA plays vital roles in joints such as hydration and lubrication, 41,42 and is clinically prescribed for OA patients due to its ability to reduce joint friction, protect joint surfaces, and provide pain relief. 12,43 Its biocompatibility and potential for chemical modification have made HA the focus of extensive research in drug delivery systems.…”

Biomimetic NO Scavenging Hyaluronic Acid Nanoparticles Enable Targeted Delivery of MTX and Integrated Management of Rheumatoid Arthritis

“…Recently, biomimetic nanoparticles with cell membrane coating have exhibited the unique advantages of excellent biocompatibility, evading the recognition of the immune system, and homologous targeting. − Neutrophils have been demonstrated to specifically migrate into the RA joints guided by the chemoattractants, adhesion molecules, and so forth and play a key role in anti-inflammation through binding and neutralizing the pro-inflammatory cytokines. , Hyaluronic acid, a natural lubricant in normal joints, is easily degraded upon free radicals and the enzyme in the RA microenvironment, thus suffering from clearance and aggravating joint damage in the setting of RA. , Based on the above, we have designed neutrophil membrane-camouflaged NO scavenging hyaluronic acid nanoparticles that can load MTX (NNO-NPs/MTX) to mediate specific and integrated therapy against RA (Scheme ). NNO-NPs/MTX were fabricated from NO-responsive HA-DABA-PLGA micelles with MTX loading in the hydrophobic core and neutrophil membrane coating on the outer surface.…”