Vasoactive intestinal peptide modified defect-engineered ZnOx-Au-NaBH4 nanoplatform inducing pyroptosis in fibroblast-like synoviocytes for therapy of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a prevalent chronic inflammatory disorder characterized by synovial hyperplasia, wherein the proliferating synovial tissue comprises fibroblast-like synoviocytes (FLS). The eradication of FLS is presently the focal point of study in the therapy of RA. Pyroptosis, a distinct form of controlled cell death, has garnered significant interest in recent study. Consequently, alongside diverse conventional therapy methods, precisely targeting the development of FLS pyroptosis and augmenting the capacity to eliminate FLS has emerged as a novel avenue for investigating RA. This study presents a unique multifunctional nanotherapeutic platform for the treatment of rheumatoid arthritis, utilizing defect-rich zinc oxide (D.ZnOx)‑gold (Au)-Sodium borohydride (NaBH4) (D. ZAN) nanoparticles. It alters the material via flawed engineering and incorporates Au nanoparticles to create a Schottky junction, thereby augmenting the efficacy of sonodynamic therapy (SDT) under the piezoelectric effect. Additionally, by releasing acid-responsive zinc ions (Zn2+) and hydrogen (H2), it activates the cysteine-dependent aspartate-specific protease (Caspase)-1 / Gasdermin D (GSDMD)-dependent pathway to induce pyroptosis in FLS. The integration of the material's photothermal impact with the targeting capability of vasoactive intestinal peptide (VIP) facilitates the accurate elimination of FLS, thereby inhibiting the growth of synovial tissues and halting the advancement of RA.