State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, Med-X Center for Materials, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, P. R. China.
West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.
J Dent Res. 2022 Jul;101(8):921-930. doi: 10.1177/00220345221085192. Epub 2022 Mar 31.
Some oral squamous cell carcinomas (OSCCs) originate from preexisting oral potentially malignant disorders (OPMDs). Oral leukoplakia (OLK) is the most common and typical OPMD in the clinic, so treatment for it is essential to reduce OSCC incidence. Local chemotherapy is an option other than surgery considering the superficial site of OLK. However, there are no standardized drugs applied to OLK, and traditionally used chemotherapeutic drugs revealed limited efficacy for lack of adhesion. Hence, there is a growing demand to prepare new agents that combine mucoadhesion with an anti-OLK effect. Here, an isoguanosine-tannic acid (isoG-TA) supramolecular hydrogel via dynamic borate esters was successfully fabricated based on isoG and TA. Previously reported guanosine-TA (G-TA) hydrogel was also explored for an anti-OLK effect. Both gels not only exhibited ideal adhesive properties but also integrated anti-OLK activities in one system. In vitro cell viability indicated that isoG and TA inhibited the proliferation of dysplastic oral keratinocytes (DOKs). The in vivo OLK model evidence revealed that both gels showed potential to prevent OLK canceration. In addition, the probable anti-DOK mechanisms of isoG and TA were investigated. The results indicated that isoG could bind to adenosine kinase (ADK) and then affected the mammalian target of rapamycin (mTOR) pathway to inhibit DOK proliferation. TA could significantly and continuously reduce reactive oxygen species (ROS) in DOKs through its antioxidant effect. ROS plays an important role in the progression of cell cycle. We proved that the low level of ROS may inhibit DOK proliferation by inducing G/G arrest in the cell cycle. Altogether, this study innovatively fabricated an isoG-TA hydrogel with ideal adhesion, and both isoG and TA showed in vitro inhibition of DOKs. Moreover, both isoG-TA and G-TA hydrogels possessed potential in delaying the malignant transformation of OLK, and the G-TA hydrogel showed a better statistical effect, providing an effective strategy for controlling OLK.
一些口腔鳞状细胞癌 (OSCC) 源自于先前存在的口腔潜在恶性疾病 (OPMD)。口腔白斑病 (OLK) 是临床上最常见和典型的 OPMD，因此治疗 OLK 对于降低 OSCC 的发生率至关重要。考虑到 OLK 的浅表位置，局部化疗是手术之外的一种选择。然而，OLK 没有标准化的药物，传统使用的化疗药物由于缺乏粘附性而显示出有限的疗效。因此，人们越来越需要制备新的药物，将粘膜粘附性与抗 OLK 效果结合起来。在这里，通过动态硼酸酯成功地制备了一种基于异鸟苷和单宁酸 (isoG-TA) 的超分子水凝胶。先前报道的鸟苷-TA (G-TA) 水凝胶也被用于抗 OLK 作用的研究。两种凝胶不仅表现出理想的粘附性能，而且在一个系统中整合了抗 OLK 活性。体外细胞活力表明，异鸟苷和单宁酸抑制了发育不良的口腔角质形成细胞 (DOK) 的增殖。体内 OLK 模型的证据表明，两种凝胶都有可能预防 OLK 的癌变。此外，还研究了异鸟苷和单宁酸对 DOK 的可能抗作用机制。结果表明，异鸟苷可以与腺苷激酶 (ADK) 结合，然后影响哺乳动物雷帕霉素靶蛋白 (mTOR) 通路，抑制 DOK 的增殖。单宁酸通过其抗氧化作用，可显著且持续地降低 DOK 中的活性氧 (ROS)。ROS 在细胞周期的进展中起着重要作用。我们证明，低水平的 ROS 通过诱导细胞周期中的 G1/G0 期阻滞可能抑制 DOK 的增殖。总之，本研究创新性地制备了一种具有理想粘附性的异鸟苷-单宁酸水凝胶，异鸟苷和单宁酸在体外均能抑制 DOK 的增殖。此外，异鸟苷-单宁酸和 G-TA 水凝胶均具有延缓 OLK 恶性转化的潜力，而且 G-TA 水凝胶的统计学效果更好，为控制 OLK 提供了一种有效的策略。
