Targeted and Combined TPCA-1-Gold Nanocage Therapy for In Vivo Treatment of Inflammatory Arthritis
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Research Article Targeted and Combined TPCA-1-Gold Nanocage Therapy for In Vivo Treatment of Inflammatory Arthritis Ziyi Wang,1 Jing Yang,1 Yang Yang,1 Xiaorong Pu,1 Jingnan Zhao,2 and Nan Zhang1,3
Received 25 August 2020; accepted 16 October 2020 Abstract. Rheumatoid arthritis (RA) is an autoimmune disease that is currently incurable. Inhibition of inflammation can prevent the deterioration of RA. 2-[(Aminocarbonyl)amino]5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) suppresses inflammation via the inhibition of nuclear factor-κ (NF-κB) signaling pathway. Gold-based therapies have been used to treat inflammatory arthritis since the 1940s. Hyaluronic acid (HA) is a targeting ligand for CD44 receptors overexpressed on activated macrophages. Therefore, a combined therapy based on TPCA-1, gold, and HA was explored for the treatment of RA in this study. We used gold nanocages (AuNCs) to load TPCA-1 and modified the TPCA-1 (T) loaded AuNCs with HA and peptides (P) to construct an anti-inflammatory nanoparticle (HAAuNCs/T/P). An adjuvant-induced arthritis (AIA) mice model was used to investigate the in vivo anti-inflammatory efficacy of HA-AuNCs/T/P. In vivo distribution results showed that HA-AuNCs/T/P had increased and prolonged accumulation at the inflamed paws of AIA mice. Treatment by the HA-AuNCs/T/P suppressed joint swelling and alleviated cartilage and bone damage. By loading to HA-AuNCs/T/P, the effective concentration of TPCA-1 was greatly reduced from 20 to 0.016 mg/kg mice. This study demonstrated that HA-AuNCs/T/P could effectively suppress inflammation and alleviate the symptoms of AIA mice, suggesting a great potential of HA-AuNCs/T/P for the treatment of RA. KEY WORDS: gold nanocages; TPCA-1; hyaluronic acid; rheumatoid arthritis.
INTRODUCTION Rheumatoid arthritis (RA) is an incurable and chronic autoimmune disease that affects approximately 1% of population worldwide (1). The early stage of RA is characterized by inflammation of joints and pathological changes of cartilage and synovium (2). Deterioration of RA causes joint deformity, bone erosion, and even organ failure and death (3). Therefore, early diagnosis and treatment of RA is very important. Although the pathogenesis of RA is not completely clear at present, many studies have shown that inflammation suppression by interfering with the activation of the nuclear factor-κ (NF-κB) pathway can halt the progress of the disease (4–7). Supplementary Information The online version contains supplementary material available at https://doi.org/10.1208/s12249-020-01856-0. 1
Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China. 2 Biotechnology G2018, School of International Education, Henan University of Technology, No. 100 Lianhua Street, Zhengzhou, 450001, China. 3 To whom correspondence should be addressed. (e–mail: [email protected])
NF-κB is a nuclear transcription factor expressed in various types of cells and plays an important role in the regulation of inflammation (8). Inhibitor of NF-κB (IκB), as
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