Targeted hexagonal Pd nanosheet combination therapy for rheumatoid arthritis via the photothermal controlled release of MTX

Abstract

Methotrexate (MTX) is a drug that is used for the clinical treatment of rheumatoid arthritis (RA), a stubborn disease caused by over-immunization. However, the toxicity that arises as a result of poor selectivity to inflammatory cells severely limits the application of MTX. Therefore, new therapeutic strategies are needed for treating RA. Here, we describe the design and synthesis of a nanotherapy agent, Pd-Cys@MTX@RGD, which can target inflammatory cells and control MTX release. The novel hexagonal palladium (Pd) nanosheets were used as a near-infrared (NIR) photothermal agent modified with arginine-glycineaspartic acid (RGD) peptides on the surface to enhance the ability of the nanosheet targeting of inflammatory cells. In subsequent experiments, the Pd-Cys@MTX@RGD nanosheets were observed to greatly reduce the toxicity of MTX, showing controlled MTX release under irradiation of 808 nm (0.3 W cm⁻²). Moreover, taking advantage of the fact that MTX can be combined with multiple therapeutic methods, the photothermal therapy (PTT) of Pd nanosheets provided a compensatory effect to enhance the therapeutic efficacy of MTX. Under combination therapy, Pd-Cys@MTX@RGD was shown to effectively inhibit the inflammatory response induced by vascular endothelial growth factor (VEGF) and IL-1β. And, in vivo, multifunctional Pd-Cys@MTX@RGD effectively inhibited the symptoms of RA by inhibiting the expression of pro-inflammatory cytokines (TNF-α,COX-2). We hope that the construction of nanomaterials can add potential value to the design of chemical drugs and therapeutic strategies for RA.