Targeted therapy for autoimmune diseases based on multifunctional frame nucleic acid system: Blocking TNF-α-NF-κB signaling and mediating macrophage polarization

肿瘤坏死因子α 巨噬细胞极化 核酸 NF-κB 阻塞(统计) 化学 信号转导 细胞生物学 免疫学 医学 巨噬细胞 计算机科学 生物 生物化学 体外 计算机网络
作者
Mei Zhang,Yuting Wen,Zhangheng Huang,Xin Qin,Mi Zhou,Dexuan Xiao,Weitong Cui,Zhiqiang Liu,Yunfeng Lin
出处
期刊:Chemical Engineering Journal [Elsevier]
卷期号:454: 140399-140399 被引量:21
标识
DOI:10.1016/j.cej.2022.140399
摘要

• MTX@Tapt-tFNAs, a novel anti-inflammatory drug based on framework nucleic acid nano delivery system, was developed to combine the dual roles of MTX and TNF-α-targeted DNA aptamer for the targeted therapy of rheumatoid arthritis. • MTX@Tapt-tFNAs show good biocompatibility, serum stability, targeting, and low toxicity. • MTX@Tapt-tFNAs exert a good anti-inflammatory effect by blocking TNF-α-NF-κB signaling and promoting M2 macrophage polarization. Rheumatoid arthritis (RA), a chronic autoimmune disease (AD), can cause irreversible loss of joint function. The methotrexate (MTX) is the first-line choice in the treatment of RA; however, its efficacy is limited due to its insolubility in water and lack of targeting ability. The development of nucleic acid nano system provides new prospect for it. Therefore, considering that tumor necrosis factor-α (TNF-α) is the cornerstone and significant target of ADs treatment, the TNF-α-targeted aptamer (Tapt)-modified tetrahedral frame nucleic acid (Tapt-tFNAs, TT) were chosen to carry MTX, which assembled into MTX-loaded Tapt-tFNA polyplexes (MTX@Tapt-tFNAs, MTT). As a carrier, tFNAs not only enhance the stability of Tapt in serum but strengthen the bioavailability of MTX. MTX@Tapt-tFNAs promote the expression of M2 macrophages and inhibit inflammatory factor infiltration by blocking the nuclear factor-κB (NF-κB) and extracellular regulated protein kinases (ERKs) signaling pathways. Moreover, MTX@Tapt-tFNAs are more concentrated in the inflammatory joints to reduce toxicity caused by systemic use of MTX, decrease collagen-induced arthritis (CIA) lesions and bone and cartilage defects. These results indicate that MTX@Tapt-tFNAs are a promising targeted nanomedicine against RA.
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