<br>MUC5AC 的活性纳米颗粒靶向改善实验性结肠炎的治疗效果,Nanoscale

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MUC5AC 的活性纳米颗粒靶向改善实验性结肠炎的治疗效果
Nanoscale ( IF 5.8 ) Pub Date : 2024-02-22 , DOI: 10.1039/d3nr05681c
Bernadette Riemann _{1,

2} , Thomas Antoine ₁ , Arnaud Béduneau ₁ , Yann Pellequer ₁ , Alf Lamprecht _{1,

2} , Brice Moulari ₁

Affiliation

炎症性肠病（IBD）包括克罗恩病（CD）和溃疡性结肠炎（UC），是胃肠道的慢性炎症性疾病，其特征是肠道慢性复发性溃疡。结肠靶向给药系统 (DDS) 因其通过改善炎症组织选择性来治疗 IBD 的潜力而受到广泛关注。在此，建议将抗MUC5AC修饰的载药纳米颗粒（NP）用于主动上皮靶向和选择性粘附实验性结肠炎中的发炎组织。通过与非靶向 BSA-NP 缀合物进行比较，测试了与抗 MUC5AC（抗 MUC5）缀合的 NP 与 HT29-MTX 细胞的生物粘附程度。在体内，在小鼠结肠炎模型中研究了生物粘附的选择性和配体密度对生物粘附效率的影响以及负载糖皮质激素的抗MUC5-NP的治疗益处。定量粘附分析表明，与用作对照的 PNA-、IgG1- 和 BSA-NP 缀合物相比，抗 MUC5 缀合的 NP 对发炎组织表现出更高的结合和选择性。人们发现这种生物粘附效率取决于纳米颗粒表面的配体密度。通过荧光成像证实了抗MUC5配体和发炎组织之间的结合特异性。抗 MUC5-NP 和所有其他含有糖皮质激素的制剂均导致实验性结肠炎的显着缓解，这从髓过氧化物酶活性和促炎细胞因子浓度（TNF-α、IL-1β）的大幅降低中可见一斑。使用抗 MUC5 靶向 NP 似乎是未来治疗影响胃肠道但不限于结肠炎的各种类型局部疾病的非常有前途的工具。

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Active nanoparticle targeting of MUC5AC ameliorates therapeutic outcome in experimental colitis

Inflammatory bowel diseases (IBDs), which include Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory diseases of the gastrointestinal tract and are characterized by chronic recurrent ulceration of the bowels. Colon-targeted drug delivery systems (DDS) have received significant attention for their potential to treat IBD by improving the inflamed tissue selectivity. Herein, antiMUC5AC-decorated drug loaded nanoparticles (NP) are suggested for active epithelial targeting and selective adhesion to the inflamed tissue in experimental colitis. NPs conjugated with antiMUC5AC (anti-MUC5) were tested for their degree of bioadhesion with HT29-MTX cells by comparison with non-targeted BSA-NP conjugates. In vivo, the selectivity of bioadhesion and the influence of ligand density in bioadhesion efficiency as well as the therapeutic benefit for glucocorticoid loaded anti-MUC5-NP were studied in a murine colitis model. Quantitative adhesion analyses showed that anti-MUC5-conjugated NP exhibited a much higher binding and selectivity to inflamed tissue compared to PNA-, IgG1- and BSA-NP conjugates used as controls. This bioadhesion efficiency was found to be dependent on the ligand density, present at the NP surface. The binding specificity between anti-MUC5 ligand and inflamed tissues was confirmed by fluorescence imaging. Both anti-MUC5-NP and all other glucocorticoid containing formulations led to a significant mitigation of the experimental colitis, as became evident from the substantial reduction of myeloperoxidase activity and pro-inflammatory cytokine concentrations (TNF-α, IL-1β). Targeted NP by using anti-MUC5 appears to be a very promising tool in future treatment of various types of local disorders affecting the gastro-intestinal tract but not limited to colitis.

更新日期：2024-02-26

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