| Autor: |
Xiaonan Wang, Fanfan Guo, Yi Zhang, Ziyi Wang, Jiaqi Wang, Rongrong Luo, Xiao Chu, Yongxing Zhao, Pengchao Sun |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
International Journal of Pharmaceutics: X, Vol 5, Iss , Pp 100162- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2590-1567 |
| DOI: |
10.1016/j.ijpx.2023.100162 |
| Popis: |
Selective suppression of tumor necrosis factor (TNF) α-TNF receptor 1 (TNFR1) signaling is a potent solution for rheumatoid arthritis (RA). Herein, novel composite nucleic acid nanodrugs that simultaneously restrain TNF α binding and TNFR1 multimerization were designed to reinforce inhibition of TNF α-TNFR1 signaling for RA therapy. Towards this end, a novel peptide Pep4‐19 that suppresses TNFR1 clustering was extracted from TNFR1. The resulting peptide and a DNA aptamer Apt2‐55, which inhibits TNF α binding, were integrally or separately anchored on DNA tetrahedron (TD) to obtain nanodrugs with different spatial distribution of Apt2‐55 and Pep4‐19 (TD-3A-3P and TD-3(A-P)). Our results showed that Pep4‐19 enhanced the viability of inflammatory L929 cells. Both TD-3A-3P and TD-3(A-P) suppressed caspase 3, reduced cell apoptosis, and inhibited FLS-RA migration. Compared to TD-3(A-P), TD-3A-3P supplied sufficient flexibility for Apt2‐55 and Pep4‐19, and showed better anti-inflammation properties. Furthermore, TD-3A-3P significantly relieved symptoms in collagen-induced arthritis (CIA) mice, and the anti-RA efficacy through intravenous injection was comparable to transdermal administration via microneedles. Overall, the work provides an effective strategy for RA treatment by dual-targeting TNFR1, and demonstrates that microneedles are promising approach to drug administration in the treatment of RA. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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