Abstract：
Curcumin, a polyphenol extracted from turmeric, is a potential alternative for the treatment of oral squamous cell carcinoma (OSCC) due to its remarkable anticancer activity and low systemic toxicity. To further enhance the anticancer activity and bioavailability of curcumin, we synthesized a curcumin analogue, AC17, by modifying the benzene ring and methylene group of curcumin. A soluble hyaluronic acid microneedle patch (AC17@HAMN) was developed to ensure accurate and safe delivery of AC17 to tumor tissues. The inhibitory effect of AC17 on OSCC cells was stronger than that of curcumin and some common analogues. Transcriptome sequencing showed that the target genes of AC17 were mainly concentrated in apoptosis, cell cycle and cell senescence pathways. Among them, AC17 induces cell cycle arrest and inhibits cell proliferation mainly by activating FOXO3 signaling. With good penetration and dissolution properties, microneedles can deliver AC17 directly to the tumor site and show good anti-tumor effect. Moreover, AC17@HAMN showed good biosafety. In summary, AC17@HAMN offers high efficiency, minimal invasiveness, and few adverse reactions. This microneedle patch holds great promise for potential clinical applications, especially for the treatment of OSCC.
摘要：
姜黄素,从姜黄中提取的多酚，由于其显着的抗癌活性和低的全身毒性，是治疗口腔鳞状细胞癌（OSCC）的潜在替代品。为了进一步提高姜黄素的抗癌活性和生物利用度，我们合成了姜黄素类似物,AC17，通过修饰姜黄素的苯环和亚甲基。开发了可溶性透明质酸微针贴片(AC17@HAMN)以确保将AC17准确和安全地递送至肿瘤组织。AC17对OSCC细胞的抑制作用强于姜黄素和一些常见类似物。转录组测序显示,AC17的靶基因主要集中在凋亡,细胞周期和细胞衰老途径。其中,AC17主要通过激活FOXO3信号传导来诱导细胞周期停滞和抑制细胞增殖。具有良好的渗透和溶解性能，微针可将AC17直接递送至肿瘤部位,表现出良好的抗肿瘤作用。此外，AC17@HAMN表现出良好的生物安全性。总之,AC17@HAMN提供高效率，最小的侵入性，不良反应少。这种微针贴片为潜在的临床应用提供了巨大的希望，尤其是OSCC的治疗。
