Hyaluronic Acid Hydrogels Hybridized With Au-Triptolide Nanoparticles for Intraarticular Targeted Multi-Therapy of Rheumatoid Arthritis

Frontiers in Pharmacology

Cheng Lu¹  Rui Liu²  Zhenglai Hua²  Qingcai Huang²  Chenxi Li²  Yurong Song²  Yuanyan Liu²  Liuchunyang Yu²  Dongjie Zhu²  Zhengjia Zhang²  Zeyu Xue²  Youwen Chen²  Aiping Lu³ 

[1] Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China;School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China;School of Chinese Medicine, Hong Kong Baptist University, Hongkong, China;

关键词: rheumatoid arthritis;    photothermal-chemo treatment;    NIR imaging;    mTOR/p70S6K pathway;    TP-PLGA-Au@RGD/HA hydrogels;   

DOI  :  10.3389/fphar.2022.849101

来源: DOAJ

【 摘 要 】

Rheumatoid arthritis (RA) is a chronic inflammatory disease, characterized by synovial inflammation in multiple joints. Triptolide (TP) is a disease-modifying anti-rheumatic drug (DMARD) highly effective in patients with RA and has anti-inflammatory properties. However, its clinical application has been limited owing to practical disadvantages. In the present study, hyaluronic acid (HA) hydrogel-loaded RGD-attached gold nanoparticles (AuNPs) containing TP were synthesized to alleviate the toxicity and increase therapeutic specificity. The hydrogels can be applied for targeted photothermal-chemo treatment and in vivo imaging of RA. Hydrogel systems with tyramine-modified HA (TA-HA) conjugates have been applied to artificial tissue models as surrogates of cartilage to investigate drug transport and release properties. After degradation of HA chains, heat was locally generated at the inflammation region site due to near-infrared resonance (NIR) irradiation of AuNPs, and TP was released from nanoparticles, delivering heat and drug to the inflamed joints simultaneously. RA can be penetrated with NIR light. Intraarticular administration of the hydrogels containing low dosage of TP with NIR irradiation improved the inflamed conditions in mice with collagen-induced arthritis (CIA). Additionally, in vitro experiments were applied to deeply verify the antirheumatic mechanisms of TP-PLGA-Au@RGD/HA hydrogels. TP-PLGA-Au@RGD/HA hydrogel treatment significantly reduced the migratory and invasive capacities of RA fibroblast-like synoviocytes (RA-FLS) in vitro, through the decrease of phosphorylation of mTOR and its substrates, p70S6K1, thus inhibiting the mTOR pathway.

【 授权许可】

Unknown