Hybrid micelles containing methotrexate-conjugated polymer and co-loaded with microRNA-124 for rheumatoid arthritis therapy

Hao, Fei; Lee, Robert J; Zhong, Lihuang; Dong, Shiyan; Yang, Chunmiao; Teng, Lirong; Meng, Qingfan; Lu, Jiahui; Xie, Jing; Teng, Lesheng

doi:10.7150/thno.32268

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Nanotheranostics 2024; 8(4): 442-457. [Abstract] [Full text] [PDF]

Nanotheranostics 2024; 8(4): 427-441. [Abstract] [Full text] [PDF]

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Theranostics 2019; 9(18):5282-5297. doi:10.7150/thno.32268 This issue Cite

Research Paper

Hybrid micelles containing methotrexate-conjugated polymer and co-loaded with microRNA-124 for rheumatoid arthritis therapy

Fei Hao¹, Robert J Lee^1,2, Lihuang Zhong¹, Shiyan Dong¹, Chunmiao Yang¹, Lirong Teng¹, Qingfan Meng¹, Jiahui Lu¹, Jing Xie¹, Lesheng Teng^1✉

1. School of Life Sciences, Jilin University, No.2699, Qianjin Street, Changchun130012, P.R. China
2. College of Pharmacy, The Ohio State University, Columbus, 500 W 12th Ave, Columbus, OH 43210, USA

Citation:

Hao F, Lee RJ, Zhong L, Dong S, Yang C, Teng L, Meng Q, Lu J, Xie J, Teng L. Hybrid micelles containing methotrexate-conjugated polymer and co-loaded with microRNA-124 for rheumatoid arthritis therapy. Theranostics 2019; 9(18):5282-5297. doi:10.7150/thno.32268. https://www.thno.org/v09p5282.htm

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Abstract

Purpose: Methotrexate (MTX) is a first-line drug for rheumatoid arthritis (RA)therapy. However, MTX monotherapy often results in irreversible joint damage due to its slow onset of action and long duration. microRNA-124 (miR-124) has shown direct bone protection activity against RA. A co-delivery system for MTX and microRNA combination may provide therapeutic synergy.

Methods: Methotrexate-conjugated polymer hybrid micelles (M-PHMs) were prepared by self-assembly of two functional amphiphilic polymers (MTX-PEI-LA and mPEG-LA) at an optimized weight ratio. Incorporation of microRNA was achieved through electrostatic interactions between microRNA and cationic polymer MTX-PEI-LA. Cellular uptake, endosome escape, biodistribution, and therapeutic efficacy of M-PHMs/miR-124 complexes were investigated and evaluated in RAW264.7 cells and a rat adjuvant-induced arthritis (AIA) model.

Results: M-PHMs/miR-124 complexes exhibited folate receptor-mediated uptake in activated RAW264.7 cells. miR-124 was able to escape from the endosome and down-regulate nuclear factor of activated T cells cytoplasmic1 (NFATc1). M-PHMs/miR-124 complexes accumulated in inflamed joints of AIA rats and showed superior therapeutic efficacy through both anti-inflammatory effect and direct bone protective effect. Combination of miR-124 and MTX in these micelles induced disease remission.

Conclusions: M-PHMs/miR-124 was highly effective against RA through therapeutic synergy. Additional studies are warranted to further investigate its therapeutic potential and delineate its mechanisms of action.

Keywords: polymeric hybrid micelles, folate receptor, methotrexate, microRNA-124, rheumatoid arthritis

Citation styles

APA

Hao, F., Lee, R.J., Zhong, L., Dong, S., Yang, C., Teng, L., Meng, Q., Lu, J., Xie, J., Teng, L. (2019). Hybrid micelles containing methotrexate-conjugated polymer and co-loaded with microRNA-124 for rheumatoid arthritis therapy. Theranostics, 9(18), 5282-5297. https://doi.org/10.7150/thno.32268.

ACS

Hao, F.; Lee, R.J.; Zhong, L.; Dong, S.; Yang, C.; Teng, L.; Meng, Q.; Lu, J.; Xie, J.; Teng, L. Hybrid micelles containing methotrexate-conjugated polymer and co-loaded with microRNA-124 for rheumatoid arthritis therapy. Theranostics 2019, 9 (18), 5282-5297. DOI: 10.7150/thno.32268.

NLM

CSE

Hao F, Lee RJ, Zhong L, Dong S, Yang C, Teng L, Meng Q, Lu J, Xie J, Teng L. 2019. Hybrid micelles containing methotrexate-conjugated polymer and co-loaded with microRNA-124 for rheumatoid arthritis therapy. Theranostics. 9(18):5282-5297.

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