Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, China.
Jilin Provincial Key Laboratory of Surgical Translational Medicine, Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
J Nanobiotechnology. 2024 Sep 18;22(1):571. doi: 10.1186/s12951-024-02792-y.
Thyroid cancer is one of the most common endocrine malignancies in clinical practice. Traditional surgery and radioactive iodine ablation have poor treatment results for poorly differentiated thyroid cancer, and there is a risk of metastasis and recurrence. In this study, caffeic acid, a natural herbal extract with certain biological activity, has been as precursor to prepare new caffeic acid carbon nanodots via a one-step hydrothermal method. The caffeic acid carbon nanodots retains part of the structure and biological activity of caffeic acid, and have good biocompatibility, water solubility and stability. The construction of the carbon nanodots could effectively improve their bio-absorption rate and the efficacy. In vitro cell experiments showed that low-dose caffeic acid carbon nanodots had a significant inhibitory effect on poorly differentiated papillary thyroid carcinoma BCPAP cells. At low concentrations of 16 µg/mL, the inhibition rate of human thyroid cancer cells BCPAP was ~ 79%. The anti-tumor mechanism was predicted and verified by transcriptome, real-time quantitative PCR and western blot experiments. The caffeic acid carbon nanodots showed to simultaneously downregulate the expression of KRAS, p-BRAF, p-MEK1 and p-ERK1/2, the four continuous key proteins in a MAPK classical signaling pathway. In vivo experiments further confirmed the caffeic acid carbon nanodots could significantly inhibit the tumorigenicity of xenografts in papillary thyroid carcinoma at quite low doses. This piece of work provides a new nanomedicine and therapeutic strategy for highly resistant poorly differentiated papillary thyroid carcinoma.
甲状腺癌是临床实践中最常见的内分泌恶性肿瘤之一。传统的手术和放射性碘消融治疗对低分化甲状腺癌的治疗效果不佳，存在转移和复发的风险。本研究以咖啡酸为天然草药提取物，具有一定的生物活性，将其作为前体，通过一步水热法制备了新型咖啡酸碳纳米点。咖啡酸碳纳米点保留了部分咖啡酸的结构和生物活性，具有良好的生物相容性、水溶性和稳定性。碳纳米点的构建可以有效提高其生物吸收率和疗效。体外细胞实验表明，低剂量的咖啡酸碳纳米点对低分化甲状腺癌 BCPAP 细胞具有显著的抑制作用。在 16μg/ml 的低浓度下，人甲状腺癌细胞 BCPAP 的抑制率约为 79%。通过转录组、实时定量 PCR 和 Western blot 实验预测和验证了抗肿瘤机制。咖啡酸碳纳米点同时下调 MAPK 经典信号通路中四个连续关键蛋白 KRAS、p-BRAF、p-MEK1 和 p-ERK1/2 的表达。体内实验进一步证实，咖啡酸碳纳米点在相当低的剂量下能显著抑制甲状腺乳头状癌异种移植瘤的致瘤性。这项工作为高度耐药的低分化甲状腺癌提供了一种新的纳米医学和治疗策略。
