口腔癌是全球死亡的主要原因之一。口腔癌前病变（OPL）是口腔癌的前体，具有不同程度的发展。四氢可亲醇（THC）是姜黄素的主要代谢产物，对各种类型的癌症具有卓越的抗癌特性。然而，THC的临床疗效受其溶解度差的限制。在此，我们开发了基于黏附蛋白酶基复合海绵的新型黏膜附着剂，用于THC的颊内给药，利用纳米技术和粘附性来高效预防和治疗口腔癌。首先，制备并表征了THC纳米晶体（THC-NC），以便将其后续装载到黏附复合海绵中。使用人类舌鳞状细胞癌细胞系（SCC-4）评估了THC-NC的抗癌活性。最后，测试了TCC-NC装载海绵（THC-NC-S）对DMBA诱导的仓鼠OPL的化学预防活性。选择的THC-NC呈现532.68±13.20nm的粒径和-46.08±1.12mV的电位。此外，THC-NC增强了对SCC-4的抗癌作用，IC50值为80µg/mL。THC-NC-S表现出良好的粘附性能（0.24±0.02N），具有持续的药物释放，在4天内释放出90%的THC。此外，THC-NC-S具有维持高化学预防活性的巨大潜力，通过明显的异型度回归和细胞周期蛋白D1减少（对照组：40.4±12.5，THC-NC-S：12.07±5.2），在治疗25天后显著改善。综上所述，新型THC-NC-S代表了一种有前景的OPL局部治疗平台，可以预防其向恶性癌变的转化。

Oral cancer is one of the leading causes of death worldwide. Oral precancerous lesions (OPL) are the precursors of oral cancer, with varying degrees of progression. Tetrahydrocurcumin (THC) is a major metabolite of curcumin with superior anticancer properties against various types of cancer. However, THC's clinical outcome is limited by its poor aqueous solubility. Herein, we developed novel mucoadhesive biopolymer-based composite sponges for buccal delivery of THC, exploiting nanotechnology and mucoadhesion for efficient prevention and treatment of oral cancer. Firstly, THC-nanocrystals (THC-NC) were formulated and characterized for subsequent loading into mucoadhesive composite sponges. The anticancer activity of THC-NC was assessed on a human tongue squamous carcinoma cell line (SCC-4). Finally, the chemopreventive activity of THC-NC loaded sponges (THC-NC-S) was examined in DMBA-induced hamster OPL. The selected THC-NC exhibited a particle size of 532.68 ± 13.20 nm and a zeta potential of -46.08 ± 1.12 mV. Moreover, THC-NC enhanced the anticancer effect against SCC-4 with an IC50 value of 80 µg/mL. THC-NC-S exhibited good mucoadhesion properties (0.24 ± 0.02 N) with sustained drug release, where 90% of THC was released over 4 days. Furthermore, THC-NC-S had a magnificent potential for maintaining high chemopreventive activity, as demonstrated by significant regression in the dysplasia degree and a decline in cyclin D1 (control: 40.4 ± 12.5, THC-NC-S: 12.07 ± 5.2), culminating in significant amelioration after 25 days of treatment. Conclusively, novel THC-NC-S represent a promising platform for local therapy of OPL, preventing their malignant transformation into cancer.