A new strategy of using low-dose caffeic acid carbon nanodots for high resistance to poorly differentiated human papillary thyroid cancer

Abstract 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.