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

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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.

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

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Publication details

The article was received on 01 Sep 2018, accepted on 10 Nov 2018 and first published on 27 Nov 2018


Article type: Paper
DOI: 10.1039/C8TB02302F
Citation: J. Mater. Chem. B, 2019, Advance Article
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    Targeted hexagonal Pd nanosheet combination therapy for rheumatoid arthritis via the photothermal controlled release of MTX

    X. Chen, X. Zhu, T. Xu, M. Xu, Y. Wen, Y. Liu, J. Liu and X. Qin, J. Mater. Chem. B, 2019, Advance Article , DOI: 10.1039/C8TB02302F

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