Dual-targeting inhibition of TNFR1 for alleviating rheumatoid arthritis by a novel composite nucleic acid nanodrug.

ABSTRACT: 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) suppre

SUBMITTER: Wang X 

PROVIDER: S-EPMC10314200 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature