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.
文章引用产品列表
-
- EK282
- ELISA试剂盒
Mouse TNF-a ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥10,800.00
-
- EK282HS
- ELISA试剂盒, 高敏试剂盒
Mouse TNF-α High Sensitivity ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥2,000.00 – ¥3,400.00
-
- EK206
- ELISA试剂盒
Mouse IL-6 ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥10,800.00
-
- EK206HS
- ELISA试剂盒, 高敏试剂盒
Mouse IL-6 High Sensitivity ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥2,000.00 – ¥3,400.00
-
- EK201BHS
- ELISA试剂盒, 高敏试剂盒
Mouse IL-1β High Sensitivity ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥2,000.00 – ¥3,400.00
-
- EK201B
- ELISA试剂盒
Mouse IL-1β ELISA Kit 检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥10,800.00