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负载甲氨蝶呤的多功能纳米颗粒用于近红外光照射治疗类风湿性关节炎。

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

作者信息

Ha You-Jung, Lee Sun-Mi, Mun Chin Hee, Kim Hyung Joon, Bae Yonghee, Lim Ji-Hee, Park Kyu-Hyung, Lee Soo-Kon, Yoo Kyung-Hwa, Park Yong-Beom

机构信息

Division of Rheumatology, Department of Internal Medicine, Institute for Immunology and Immunologic Diseases, Yonsei University College of Medicine, 50, Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Nanomedical Graduate Program, Yonsei University, Seoul, Republic of Korea.

出版信息

Arthritis Res Ther. 2020 Jun 18;22(1):146. doi: 10.1186/s13075-020-02230-y.

DOI:10.1186/s13075-020-02230-y
PMID:32552859
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7302395/
Abstract

BACKGROUNDS

Despite the advances of rheumatoid arthritis (RA) therapeutics, several patients do not receive adequate treatment due to the toxicity and/or insufficient response of drugs. The aim of this study is to design photothermally controlled drug release from multifunctional nanoparticles (MNPs) at a near-infrared (NIR) irradiated site to improve therapeutic efficacy for RA and reduce side effects.

METHODS

Au film was deposited onto methotrexate (MTX)-loaded poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PLGA) nanoparticles, resulting in MTX-loaded MNPs. The synergistic effects of MTX-loaded MNPs with NIR irradiation were investigated using RA fibroblast-like synoviocytes (FLSs) and collagen-induced arthritis (CIA) mice.

RESULTS

Upon NIR irradiation, NIR resonance of the Au half-shell generated heat locally, accelerating MTX release from PLGA nanoparticles. In vivo NIR images of MTX-loaded MNPs indicated effective delivery of the MNPs to the inflamed joints. Moreover, in collagen-induced arthritis mice, MTX-loaded MNPs containing 1/1400 of MTX solution (repeated-dose administration) had therapeutic effects comparable to conventional treatment with MTX solution. In vitro experiments showed higher therapeutic efficacy of MTX-loaded MNPs with NIR irradiation than that of chemotherapy alone.

CONCLUSIONS

A combination therapy of MTX-loaded MNP and NIR irradiation showed durable and good treatment efficacy for the suppression of arthritis in a single administration of small dose of MTX. Our results demonstrate that the treatment modality using drug-loaded MNP with NIR irradiation may be a promising therapeutic strategy for the treatment of RA and allow in vivo NIR optical imaging.

摘要

背景

尽管类风湿关节炎（RA）治疗取得了进展，但由于药物毒性和/或反应不足，仍有部分患者未得到充分治疗。本研究旨在设计在近红外（NIR）照射部位从多功能纳米颗粒（MNP）进行光热控制药物释放，以提高RA治疗效果并减少副作用。

方法

将金膜沉积在负载甲氨蝶呤（MTX）的聚（乙二醇）-聚（乳酸-乙醇酸）（PLGA）纳米颗粒上，得到负载MTX的MNP。使用RA成纤维细胞样滑膜细胞（FLS）和胶原诱导性关节炎（CIA）小鼠研究负载MTX的MNP与NIR照射的协同作用。

结果

在NIR照射下，金半壳的NIR共振在局部产生热量，加速MTX从PLGA纳米颗粒中释放。负载MTX的MNP的体内NIR图像表明MNP有效递送至炎症关节。此外，在胶原诱导性关节炎小鼠中，含有1/1400 MTX溶液（重复给药）的负载MTX的MNP具有与MTX溶液常规治疗相当的治疗效果。体外实验表明，NIR照射下负载MTX的MNP比单独化疗具有更高的治疗效果。

结论

负载MTX的MNP与NIR照射的联合治疗在单次小剂量MTX给药中对关节炎的抑制显示出持久且良好的治疗效果。我们的数据表明，使用负载药物的MNP与NIR照射的治疗方式可能是治疗RA的一种有前景的治疗策略，并允许进行体内NIR光学成像。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff5b/7302395/09f5a48ad49d/13075_2020_2230_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff5b/7302395/7e8dfca5af59/13075_2020_2230_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff5b/7302395/fba62c28c943/13075_2020_2230_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff5b/7302395/1002d9564293/13075_2020_2230_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff5b/7302395/bc95cc5abb62/13075_2020_2230_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff5b/7302395/b44830481de7/13075_2020_2230_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff5b/7302395/09f5a48ad49d/13075_2020_2230_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff5b/7302395/7e8dfca5af59/13075_2020_2230_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff5b/7302395/fba62c28c943/13075_2020_2230_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff5b/7302395/1002d9564293/13075_2020_2230_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff5b/7302395/bc95cc5abb62/13075_2020_2230_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff5b/7302395/b44830481de7/13075_2020_2230_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff5b/7302395/09f5a48ad49d/13075_2020_2230_Fig6_HTML.jpg

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