Gold-thiol-beaded albumin nanoparticles for chemo-combined pulsatile plasmonic laser therapy of Rheumatoid arthritis in rat model

Rheumatoid arthritis (RA) is a chronic inflammatory immune disease that causes synovial membrane inflammation and destruction of articular cartilage. Traditionally, methotrexate is a first-line drug for RA treatment. However, its therapeutic benefits are insufficient. Pulsatile Plasmonic laser therapy (PPLT) has recently emerged as a localized and new-generation intervention for RA. This investigation reports the development of nanoGold-thiol-beaded albumin nanoparticles containing Leflunomide (GTBA-NP-L; 54 nm, PDI: 0.15 and entrapment efficiency: >90 %) for treating RA in an arthritic rat model. Upon irradiation of the plasmonic laser, the nanoGold component of GTBA-NP-L showed a local thermogenic effect (1.5 W/cm² for 5 mins: ∼45 °C). This local thermal effect enhances drug release (1.5-fold) while co-delivering heat and antiarthritic leflunomide at inflamed RA joints site. In vitro and in vivo studies demonstrated significant antiarthritic effects of GTBA-NP-L, accompanied by reduced inflammatory stress in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cells and antigen-induced arthritis (AIA) rat model. GTBA-NP-L treatment significantly reduced the cell viability (49.66 ± 2.46 %), apoptosis (83.36 ± 4.30 %), cell cycle arrest (38.28 ± 2.85 %), ROS and Nitrite stress levels (178.92 ± 19.79 %), and suppressed pro-inflammatory cytokines (TNF-α: 4.81, IL-6: 3.07 and IL-1β: 4.46-fold). In the arthritic rat, GTBA-NP-L treatment reduced inflammation, paw edema (1.89-fold), pain perception (45–48 %), and impacted hematological (Hb and RBCs: 12–15 %, WBCs: 30–32 %), serological (RF: 50–54 %, CRP: 40–47 %), and radiological parameters. Conclusively, the study demonstrates that the chemo-combined Pulsatile Plasmonic laser therapy showed superior efficacy as compared to individual treatments, suggesting GTBA-NP-L as a potential therapeutic candidate for rheumatoid arthritis.