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Theranostics 2020; 10(19):8479-8493. doi:10.7150/thno.46761 This issue Cite

Research Paper

Yeast Cell wall Particle mediated Nanotube-RNA delivery system loaded with miR365 Antagomir for Post-traumatic Osteoarthritis Therapy via Oral Route

Long Zhang1✉, Hang Peng2, Wan Zhang2, Yankun Li2, Liang Liu3, Tongtong Leng1

1. Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, PR China.
2. Health Science Center of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
3. Department of Orthopaedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.

✉ Corresponding author: E-mail: zhlong990xjtu.edu.cn; Phone: +8602985324587.

Citation:
Zhang L, Peng H, Zhang W, Li Y, Liu L, Leng T. Yeast Cell wall Particle mediated Nanotube-RNA delivery system loaded with miR365 Antagomir for Post-traumatic Osteoarthritis Therapy via Oral Route. Theranostics 2020; 10(19):8479-8493. doi:10.7150/thno.46761. https://www.thno.org/v10p8479.htm
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Abstract

Graphic abstract

Post-traumatic osteoarthritis (PTOA) is an acute injury-induced joint inflammation followed by a gradual degradation of articular cartilage. However, there is no FDA-approved Disease-Modifying Osteoarthritis Drug currently. Although gene therapy with microRNA can improve PTOA progression, there is no effective gene delivery vehicle for orally deliver therapeutics due to the harsh environment of the gastrointestinal tract. In this study, we investigated the effect of yeast cell wall particle (YCWP) mediated nanotube-RNA delivery system on PTOA therapy via oral route.

Methods: Nontoxic and degradable AAT and miRNA365 antagomir was self-assembled into miR365 antagomir/AAT (NPs). Then NPs-YCWP oral drug delivery system was constructed by using NPs and non-pathogenic YCWP which can be specifically recognized by macrophages. Moreover, surgical destabilization of the medial meniscus induced PTOA mice model was established to evaluate the therapeutic effect of NPs-YCWP via oral route.

Results: Compared with control group, NPs showed higher gene inhibition efficiency both in chondrogenic cell line and primary chondrocytes in vitro. Treatment of macrophages with fluorescently labeled NPs-YCWP, the results showed that NPs-YCWP was successfully engulfed by macrophages and participated in the regulation of gene expression in vitro. Under the protection of YCWP, miR365 antagomir/AAT passes through the gastrointestinal tract without degradation after oral administration. After NPs-YCWP therapy, the results of histological staining, gene and protein expression showed that miR365 antagomir/NPs-YCWP improved the symptom of PTOA.

Conclusion: Here, we constructed a biodegradable drug delivery system based on non-pathogenic YCWP and nanotubes, which can be used for PTOA therapy via the oral route. It suggests a new gene therapy strategy with YCWP mediated oral nano drug delivery system may serve as a platform for joint degeneration treatment.

Keywords: yeast cell wall particle, PTOA, gene therapy, oral drug delivery, macrophage

Citation styles

APA
Zhang, L., Peng, H., Zhang, W., Li, Y., Liu, L., Leng, T. (2020). Yeast Cell wall Particle mediated Nanotube-RNA delivery system loaded with miR365 Antagomir for Post-traumatic Osteoarthritis Therapy via Oral Route. Theranostics, 10(19), 8479-8493. https://doi.org/10.7150/thno.46761.

ACS
Zhang, L.; Peng, H.; Zhang, W.; Li, Y.; Liu, L.; Leng, T. Yeast Cell wall Particle mediated Nanotube-RNA delivery system loaded with miR365 Antagomir for Post-traumatic Osteoarthritis Therapy via Oral Route. Theranostics 2020, 10 (19), 8479-8493. DOI: 10.7150/thno.46761.

NLM
Zhang L, Peng H, Zhang W, Li Y, Liu L, Leng T. Yeast Cell wall Particle mediated Nanotube-RNA delivery system loaded with miR365 Antagomir for Post-traumatic Osteoarthritis Therapy via Oral Route. Theranostics 2020; 10(19):8479-8493. doi:10.7150/thno.46761. https://www.thno.org/v10p8479.htm

CSE
Zhang L, Peng H, Zhang W, Li Y, Liu L, Leng T. 2020. Yeast Cell wall Particle mediated Nanotube-RNA delivery system loaded with miR365 Antagomir for Post-traumatic Osteoarthritis Therapy via Oral Route. Theranostics. 10(19):8479-8493.

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