PDF(Pubmed)
Abstract：
Oral leukoplakia (OLK) is the most common oral precancerous lesion, and 3%-17% of OLK patients progress to oral squamous cell carcinoma. OLK is susceptible to recurrence and has no effective treatment. However, conventional drugs have significant side effects and limitations. Therefore, it is important to identify drugs that target OLK. In this study, scavenger receptor A (SR-A) was found to be abnormally highly expressed in the oral mucosal epithelial cells of OLK patients, whereas molecular biology studies revealed that low molecular weight fucoidan (LMWF) promoted apoptosis of dysplastic oral keratinocytes (DOK) and inhibited the growth and migration of DOK, and the inhibitory effect of LMWF on OLK was achieved by regulating the SR-A/Wnt signaling axis and related genes. Based on the above results and the special situation of the oral environment, we constructed LMWF/poly(caprolactone-co-lactide) nanofiber membranes with different structures for the in-situ treatment of OLK using electrospinning technology. The results showed that the nanofiber membranes with a shell-core structure had the best physicochemical properties, biocompatibility, and therapeutic effect, which optimized the LMWF drug delivery and ensured the effective concentration of the drug at the target point, thus achieving precise treatment of local lesions in the oral cavity. This has potential application value in inhibiting the development of OLK.
摘要：
口腔白斑（OLK）是最常见的口腔癌前病变，3％-17％的OLK患者进展为口腔鳞状细胞癌。OLK易复发，无有效治疗方法。然而,常规药物有明显的副作用和局限性。因此,确定靶向OLK的药物很重要。在这项研究中,发现清道夫受体A（SR-A）在OLK患者的口腔粘膜上皮细胞中异常高表达，而分子生物学研究表明，低分子量岩藻依聚糖（LMWF）促进口腔角质形成细胞（DOK）的凋亡并抑制DOK的生长和迁移，LMWF对OLK的抑制作用是通过调节SR-A/Wnt信号轴和相关基因来实现的。基于以上结果和口腔环境的特殊情况，我们构建了具有不同结构的LMWF/聚（己内酯-丙交酯）纳米纤维膜，用于使用静电纺丝技术原位处理OLK。结果表明,具有壳核结构的纳米纤维膜具有最佳的理化性质,生物相容性，和治疗效果，优化了LMWF给药方式,保证了药物在目标点的有效浓度,从而实现对口腔局部病变的精准治疗。这对于抑制OLK的发展具有潜在的应用价值。
