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

作者信息

Li Chenxi, Liu Rui, Song Yurong, Chen Youwen, Zhu Dongjie, Yu Liuchunyang, Huang Qingcai, Zhang Zhengjia, Xue Zeyu, Hua Zhenglai, Lu Cheng, Lu Aiping, Liu Yuanyan

机构信息

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.

出版信息

Front Pharmacol. 2022 May 27;13:849101. doi: 10.3389/fphar.2022.849101. eCollection 2022.


DOI:10.3389/fphar.2022.849101
PMID:35712709
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9197263/
Abstract

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 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, 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) , through the decrease of phosphorylation of mTOR and its substrates, p70S6K1, thus inhibiting the mTOR pathway.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/00fa316078da/fphar-13-849101-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/268af07a8bf0/fphar-13-849101-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/a55792d8c054/fphar-13-849101-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/c73dbd20471a/fphar-13-849101-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/b916a8c71f7d/fphar-13-849101-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/29244618ce02/fphar-13-849101-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/9d86f1f7bb9f/fphar-13-849101-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/c6eaf58ad28d/fphar-13-849101-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/518c62623b2b/fphar-13-849101-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/00fa316078da/fphar-13-849101-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/268af07a8bf0/fphar-13-849101-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/a55792d8c054/fphar-13-849101-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/c73dbd20471a/fphar-13-849101-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/b916a8c71f7d/fphar-13-849101-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/29244618ce02/fphar-13-849101-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/9d86f1f7bb9f/fphar-13-849101-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/c6eaf58ad28d/fphar-13-849101-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/518c62623b2b/fphar-13-849101-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4480/9197263/00fa316078da/fphar-13-849101-g009.jpg

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引用本文的文献

[1]
Pharmacological Inhibition of the PI3K/AKT/mTOR Pathway in Rheumatoid Arthritis Synoviocytes: A Systematic Review and Meta-Analysis (Preclinical).

Pharmaceuticals (Basel). 2025-8-2

[2]
Combating Traumatic Brain Injury: A Dual-Mechanism Hydrogel Delivering Salvianolic Acid A and Hydroxysafflor Yellow A to Block TLR4/NF-κB and Boost Angiogenesis.

Polymers (Basel). 2025-7-9

[3]
Locally Injectable Chitosan/β-Glycerophosphate Hydrogel Doped with Triptolide-Human Serum Albumin Nanoparticles for Treating Rheumatoid Arthritis.

Pharmaceuticals (Basel). 2024-10-1

[4]
Collision of herbal medicine and nanotechnology: a bibliometric analysis of herbal nanoparticles from 2004 to 2023.

J Nanobiotechnology. 2024-4-1

[5]
Arthritic Microenvironment-Dictated Fate Decisions for Stem Cells in Cartilage Repair.

Adv Sci (Weinh). 2023-9

[6]
Hydrogels for the treatment of rheumatoid arthritis.

Front Bioeng Biotechnol. 2022-10-12

本文引用的文献

[1]
Recent Progress of RGD Modified Liposomes as Multistage Rocket Against Cancer.

Front Pharmacol. 2022-1-25

[2]
Function and Mechanism of RGD in Bone and Cartilage Tissue Engineering.

Front Bioeng Biotechnol. 2021-12-15

[3]
Gold nanoparticle-mediated bubbles in cancer nanotechnology.

J Control Release. 2021-2-10

[4]
Tripterygium Ingredients for Pathogenicity Cells in Rheumatoid Arthritis.

Front Pharmacol. 2020-10-2

[5]
A review on the wide range applications of hyaluronic acid as a promising rejuvenating biomacromolecule in the treatments of bone related diseases.

Int J Biol Macromol. 2020-12-15

[6]
One-pot synthesis of hyaluronic acid-coated gold nanoparticles as SERS substrate for the determination of hyaluronidase activity.

Mikrochim Acta. 2020-10-10

[7]
HBO-PC Promotes Locomotor Recovery by Reducing Apoptosis and Inflammation in SCI Rats: The Role of the mTOR Signaling Pathway.

Cell Mol Neurobiol. 2021-10

[8]
Methotrexate-loaded multifunctional nanoparticles with near-infrared irradiation for the treatment of rheumatoid arthritis.

Arthritis Res Ther. 2020-6-18

[9]
miR-145 Inhibits Th9 Cell Differentiation by Suppressing Activation of the PI3K/Akt/mTOR/p70S6K/HIF-1α Pathway in Malignant Ascites from Liver Cancer.

Onco Targets Ther. 2020-5-5

[10]
Effect of electrical stimulation on chondrogenic differentiation of mesenchymal stem cells cultured in hyaluronic acid - Gelatin injectable hydrogels.

Bioelectrochemistry. 2020-8

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